Interleukin Expression - Proteins > Extracellular Proteins > Extracellular Ligands > Interleukins - Reviews - Review Articles on Protein Expression, Structure, Function, and Interactions

Reviews > Proteins > Extracellular Proteins > Extracellular Ligands > Interleukins > Interleukin Expression

Interleukin Expression

Published by Anonymous on 2007/9/30 (5354 reads)

1: Nat Rev Immunol. 2007 Feb;7(2):144-54.

Interleukin-7 receptor expression: intelligent design.

Mazzucchelli R, Durum SK.

Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 560, Room 31-71, Frederick, Maryland 21702-1201, USA.

Interleukin-7 (IL-7) is produced by stromal cells in lymphoid tissues and is required for the development of T cells and for their persistence in the periphery. Unlike many other cytokines that act on lymphocytes, IL-7 production by stromal cells is not substantially affected by extrinsic stimuli. So, the amount of available IL-7 protein is thought to be regulated by the rate that it is scavenged by T cells. As we review here, there is mounting evidence indicating that the amount of IL-7 receptor expressed on a cell not only determines how vigorously the cell responds to IL-7, but it can also determine how efficiently the cell consumes IL-7 and, therefore, affect the supply of this limiting resource in the niche.

Publication Types:
Review

PMID: 17259970 [PubMed - indexed for MEDLINE]

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2: Vitam Horm. 2006;74:105-45.

Control of interleukin-2 gene transcription: a paradigm for inducible, tissue-specific gene expression.

Bunting K, Wang J, Shannon MF.

Division of Molecular Bioscience, John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia.

Interleukin-2 (IL-2) is a key cytokine that controls immune cell function, in particular the adaptive arm of the immune system, through its ability to control the clonal expansion and homeostasis of peripheral T cells. IL-2 is produced almost exclusively by T cells in response to antigenic stimulation and thus provides an excellent example of a cell-specific inducible gene. The mechanisms that control IL-2 gene transcription have been studied in detail for the past 20 years and our current understanding of the nature of the inducible and tissue-specific controls will be discussed.

Publication Types:
Review

PMID: 17027513 [PubMed - indexed for MEDLINE]

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3: Pol Merkur Lekarski. 2005 Jun;18(108):724-7.

[Role of tumor necrosis factor (TNF) and interleukin-6 (IL-6) in the pathogenesis of late complications of menopause. Effects of hormone replacement therapy on TNF and IL-6 expression]

[Article in Polish]

Rachoń D.

Zakład Immunologii, AM w Gdańsku. drachon@amg.gda.pl

Tumor necrosis factor (TNF) and interleukin-6 (IL-6) are pleiotropic cytokines produced by immune and nonimmune cells. Inappropriate expression and production of TNF and IL-6 is thought to be involved in the pathogenesis of numerous diseases, including atherosclerosis which leads to coronary heart disease, osteoporosis and Alzheimer's disease. Conversely, these disorders belong to the late complications of menopause and hormone replacement therapy (HRT) may successfully improve them. Several studies have shown that postmenopausal women show an enhanced expression of TNF and IL-6. On contrary, the use of hormone replacement therapy by postmenopausal women has been shown to down regulate this overexpression. Therefore, the mechanisms underlying the protective effects of HRT can also be attributed to its immunomodulating properties which seem to restore cytokine homeostasis in postmenopausal women.

Publication Types:
English Abstract
Research Support, Non-U.S. Gov't
Review

PMID: 16124393 [PubMed - indexed for MEDLINE]

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4: Drug News Perspect. 2005 May;18(4):257-61.

Peroxisome proliferator-activated receptor gamma and its ligands in controlling interleukin-1beta target gene expression: a confusing story.

François M, Richette P, Corvol MT.

Institut National de la Santé et de la Recherche Médicale, Université Paris, Paris, France.

Antiinflammatory effects by peroxisome proliferator-activated receptor gamma (PPARgamma) agonists have been previously reported. However, PPARgamma dependency and the molecular mechanism involved in these effects require more investigation to clearly demonstrate whether PPARgamma is a key modulator of the antiinflammatory process. This would permit the design of more specific agonists or antagonists able to address the gamma subtype without cross reactions with other transcription factors, thus preventing undesirable side effects. However, several hurdles need to be taken into consideration, such as the coexpression of several PPAR isotypes in the same cell type. As PPARgamma and -alpha seem to play equal antiinflammatory roles, determining the subset of specific PPAR subtype target genes appears to be crucial. The work described here is our current understanding of the modulations of interleukin-1 target gene expression by PPARgamma and its ligands. 2005 Prous Science. All rights reserved

Publication Types:
Review

PMID: 16034482 [PubMed - indexed for MEDLINE]

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5: Asian J Androl. 2004 Jun;6(2):149-53.

Molecular identity, expression and functional analysis of interleukin-1alpha and its isoforms in rat testis.

Sultana T, Svechnikov KV, Gustafsson K, Wahlgren A, Tham E, Weber G, Soder O.

Department of Biological and Biomedical Sciences, Faculty of Health Sciences, Aga Khan University, Stadium Road, P.O. Box 3500, Karachi- 74800, Pakistan. taranum.sultana@aku.edu

Interleukin-1alpha (IL-1alpha) is a proinflammatory cytokine that has also been found to act as a paracrine mediator involved in the regulation of testicular functions. The present review provides an overview of the role of IL-1alpha in testicular physiology. Bioactive IL-1alpha isolated from adult rat testis was found to consist of three distinct immunoreactive protein species with apparent sizes of 45, 24 and 19 kDa. These isoforms showed bioactivity in a thymocyte proliferation and steroidogenesis assays with different biopotencies. The background of the molecular heterogeneity and processing, secretion and regulation of the isoforms of testicular IL-1alpha are discussed. All three isoforms have been found to be secreted into the testis tubular lumen and interstitial space. We have provided evidence that IL-1alpha is a paracrine factor that may be of importance in, e.g., the regulation of Leydig cell steroidogenesis. Pathophysiologically, testicular IL-1alpha may contribute to testicular relapse of acute lymphocytic leukemia in boys.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 15154090 [PubMed - indexed for MEDLINE]

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6: J Leukoc Biol. 2004 Aug;76(2):322-32. Epub 2004 May 3.

Regulation of interleukin-12 gene expression and its anti-tumor activities by prostaglandin E2 derived from mammary carcinomas.

Mitsuhashi M, Liu J, Cao S, Shi X, Ma X.

Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA.

Interleukin-12 (IL-12)-mediated immune responses are critical for the control of malignant development. Tumors can actively resist detrimental immunity of the host via many routes. Prostaglandin E2 (PGE2) is one of the major immune-suppressive factors derived from many types of tumors. Here, we show that systemic administration of recombinant IL-12 could therapeutically control the growth of aggressive TS/A and 4T1 mouse mammary carcinomas. However, PGE2 produced by tumors potently inhibits the production of endogenous IL-12 at the level of protein secretion, mRNA synthesis, and transcription of the constituent p40 and p35 genes. The inhibition can be reversed by NS-398, a selective inhibitor of the enzymatic activity of cyclooxygenase 2 in PGE2 synthesis. Moreover, PGE2-mediated inhibition of IL-12 production requires the functional cooperation of AP-1 and AP-1 strongly suppresses IL-12 p40 transcription. Blocking PGE2 production in vivo results in a marked reduction in lung metastasis of 4T1 tumors, accompanied by enhanced ability of peritoneal macrophages to produce IL-12 and spleen lymphocytes to produce interferon-gamma. This study contributes to the elucidation of the molecular mechanisms underlying the interaction between a progressive malignancy and the immune defense apparatus.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 15123779 [PubMed - indexed for MEDLINE]

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7: Hua Xi Yi Ke Da Xue Xue Bao. 2001 Jun;32(2):204-7.

[The effects of adenosine, interleukin-1 and theophylline on the expression of A2 adenosine receptor mRNAs in peripheral blood mononuclear cells from asthmatic patients]

[Article in Chinese]

Zhou X, Wang Z, Lin Y, Zhu Y.

Department of Respiratory Medicine, First Affiliated Hospital, WCUMS, Chengdu 610041, China.

OBJECTIVE: To explore the roles of A2a and A2b adenosine receptors(A2aAR and A2bAR) in the pathogenesis of bronchial asthma. METHODS: Eleven asthmatics and 11 healthy subjects were included in this investigation. Peripheral blood mononuclear cells(PBMCs) were obtained after density centrifugation on Ficoll-Hypaque. The expression of A2aAR and A2bAR mRNAs in PBMCs was examined by use of the reverse transcription-polymerase chain reaction (RT-PCR) and image pattern analysis semiquantitation method. RESULTS: The expression of A2aAR mRNA in PBMCs from asthmatics was not enhanced, compared with that of healthy subjects(P > 0.05). Adenosine or IL-1 or theophylline was not observed to have effect on A2aAR mRNA (P > 0.05). A2bAR gene expression in PBMCs was more markedly in patients with asthma than in normal individuals (P < 0.05). Adenosine and IL-1 significantly increased A2bAR mRNAs in asthmatics. Theophylline inhibited A2bAR gene expressions. The expression of A2bAR mRNA in PBMCs was positively correlated to serum total immunoglobulin E (TIgE) level in asthmatics (r = 0.72, P < 0.01). The expressions of A2bAR mRNA elevated by adenosine or IL-1 were correlated positively with serum TIgE(r = 0.78 or r = 0.61; P < 0.05) and negatively with the forced expiratory volume in first second to predicted value ratio (FEV1%) (r = -0.62 or r = -0.81; P < 0.05) in asthmatics. CONCLUSION: These results indicated that the expression of A2bAR mRNAs in PBMCs was more remarkable in asthmatics than in healthy subjects; that adenosine or IL-1 potentiated the mRNA expression of A2bAR in PBMCs in asthmatic patients, which was correlated with allergy state and the degree of airway obstruction; and that theophylline might antagonize adenosine by inhibiting A2bAR mRNA.

Publication Types:
English Abstract
Research Support, Non-U.S. Gov't
Review

PMID: 12600086 [PubMed - indexed for MEDLINE]

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8: Pathobiology. 2002-2003;70(3):143-9.

Neutrophil migration across the intestinal epithelial barrier--summary of in vitro data and description of a new transgenic mouse model with doxycycline-inducible interleukin-8 expression in intestinal epithelial cells.

Kucharzik T, Williams IR.

Department of Medicine B, University of Münster, Münster, Germany. ykucharz@uni-muenster.de

The intestinal epithelium serves as a protective barrier between the gut lumen and the underlying mucosa. During intestinal inflammation in inflammatory bowel disease (IBD) there is increased paracellular permeability and strong migration of the neutrophils into the mucosa as well as transepithelial neutrophil migration with the formation of crypt abscesses. From in vitro data we know that neutrophil migration is triggered by epithelial-derived interleukin-8 (IL-8). A pathogen-elicited epithelial chemoattractant activity, which is released by intestinal epithelial cells from the apical surface, seems to be responsible for the final step in transepithelial migration. To mimic the pathophysiological situation with influx of neutrophils during IBD, a double transgenic mouse model with doxycycline-inducible IL-8 expression in intestinal epithelial cells was established. This model will allow to study the role of neutrophil influx during chronic intestinal inflammation. It will also provide insights into the mechanisms of neutrophil transepithelial migration. Copyright 2003 S. Karger AG, Basel

Publication Types:
Review

PMID: 12571418 [PubMed - indexed for MEDLINE]

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9: J Leukoc Biol. 2002 Nov;72(5):847-55.

Multiple control of interleukin-8 gene expression.

Hoffmann E, Dittrich-Breiholz O, Holtmann H, Kracht M.

Institute of Pharmacology, Medical School Hannover, Germany.

Interleukin (IL)-8, a prototypic human chemokine, was detected more than a decade ago as the founding member of the chemokine superfamily. One of the most remarkable properties of IL-8 is the variation of its expression levels. In healthy tissues, IL-8 is barely detectable, but it is rapidly induced by ten- to 100-fold in response to proinflammatory cytokines such as tumor necrosis factor or IL-1, bacterial or viral products, and cellular stress. Recently, significant advances in the understanding of signaling pathways, which coordinately regulate IL-8 transcription as well as mRNA stabilization in response to external stimuli, have been made. Maximal IL-8 amounts are generated by a combination of three different mechanisms: first, derepression of the gene promoter; second, transcriptional activation of the gene by nuclear factor-kappaB and JUN-N-terminal protein kinase pathways; and third, stabilization of the mRNA by the p38 mitogen-activated protein kinase pathway. In that way, cells are able to rapidly increase and at the same time, to fine-tune the amount of IL-8 secreted and thereby control the extent of leukocytes attracted to sites of tissue injury.

Publication Types:
Review

PMID: 12429706 [PubMed - indexed for MEDLINE]

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10: J Neuroimmunol. 2002 Apr;125(1-2):5-14.

Expression and regulation of interleukin-1 receptors in the brain. Role in cytokines-induced sickness behavior.

Parnet P, Kelley KW, Bluthé RM, Dantzer R.

Laboratory of Integrative Neurobiology, INRA-INSERM U394, Institut François Magendie, Rue Camille Saint-Saens, 33077 Bordeaux Cedex, France. patricia.parnet@bordeaux.inserm.fr

Sickness behavior refers to the coordinated set of behavior changes that develop in sick individuals during the course of an infection. At the molecular level, these changes are due to the effects of proinflammatory cytokines as interleukin-1 on the brain. The purpose of this article is not to review the entire field of cytokines and behavior, but rather to address the role of interleukin-1 receptors (IL-1Rs) in sickness behavior. We briefly describe the notion of sickness behavior and present the distribution of IL-1Rs in the central nervous system of the human, mouse and rat. We then bring arguments in favor of the functionality of the various subtypes of receptors and evaluate the nature of the signaling pathways activated by brain IL-1Rs to initiate central modifications leading to symptoms of sickness. Finally, modulation of IL-1 action on its receptor by various opposing factors including glucocorticoids and anti-inflammatory cytokines is discussed.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 11960635 [PubMed - indexed for MEDLINE]

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11: J Interferon Cytokine Res. 2001 Aug;21(8):553-66.

Regulation of interleukin-8 expression by tumor-associated stress factors.

Shi Q, Xiong Q, Le X, Xie K.

Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

Tumor and host cells frequently express interleukin-8 (IL-8). IL-8 has been shown to be motogenic, mitogenic, and angiogenic and to play important roles in human tumor progression. IL-8 expression can be induced by numerous stress factors present in the tumor environment, such as hypoxia, acidosis, hyperglycemia, hyperosmotic pressure, high cell density, hyperthermia, radiation, and chemotherapeutic agents. Understanding the mechanisms of IL-8 expression and regulation will be helpful in designing potential therapeutic modalities targeting IL-8 to control tumor growth and metastasis.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 11559433 [PubMed - indexed for MEDLINE]

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12: Ann N Y Acad Sci. 2000;917:597-607.

Interleukin-1 beta and thymic peptide regulation of pituitary and glial cell cytokine expression and cellular proliferation.

Spangelo BL, Farrimond DD, Pompilius M, Bowman KL.

Department of Chemistry, University of Nevada, Las Vegas, 4505 Maryland Parkway, Las Vegas, NV 89154-4003, USA. spangelb@nevada.edu

Interleukin-6 (IL-6) is a B-cell differentiating and T-cell activating cytokine that is expressed in T cells, neutrophils, monocytes, macrophages, and mast cells. Because IL-6 is also synthesized and released by anterior pituitary cells and IL-6 stimulates pituitary hormone release, this cytokine may serve a paracrine or autocrine role within the pituitary. Interleukin-1 beta (IL-1 beta) stimulates IL-6 release from anterior pituitary cells through a mechanism that involves lysophosphatidylcholine (LPC 18:0) generation and protein kinase C activation. In the rat C6 glioma cell line, IL-1 beta synergistically stimulates IL-6 release in the presence of increased intracellular cAMP concentrations. The catecholamines and serotonin also synergistically stimulate IL-6 release in the presence of IL-1 beta. LPC 18:0 synergistically increases IL-6 release in the presence of norepinephrine, and IL-1 beta transiently increases LPC 18:0 formation in C6 cells. Therefore, IL-1 beta induction of LPC 18:0 may lead to increases in IL-6 production via activation of a kinase cascade. The bovine thymic preparation, thymosin fraction 5 (TF5), also stimulates IL-6 release from C6 glioma cells in a protein kinase C-dependent manner. Of interest, TF5 inhibits the proliferation of C6 cells, pituitary adenoma MMQ cells, and promyelocytic HL-60 cells. We suggest that a thymic hormone immune surveillance mechanism may suppress neuroendocrine and hematopoietic tumor formation. Thus, IL-1 beta and certain thymic peptides act to increase IL-6 expression in neuroendocrine cells. The enhanced production of neuroendocrine cytokines may affect hormone secretion, neurotransmission, and the development of certain neurodegenerative disorders (e.g., Alzheimer's disease). The isolation of the active component of TF5 that inhibits neuroendocrine and hematopoietic tumor cell proliferation will provide a potential therapeutic strategy for the treatment of these tumors.

Publication Types:
Review

PMID: 11268388 [PubMed - indexed for MEDLINE]

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13: Leuk Lymphoma. 2000 Sep;39(1-2):51-5.

Proliferation of immature myeloma cells by interleukin-6 is associated with CD45 expression in human multiple myeloma.

Ishikawa H, Mahmoud MS, Fujii R, Abroun S, Kawano MM.

Department of Immunohematology, Yamaguchi University School of Medicine, Ube, Japan. hishika@po.cc.yamaguchi-u.ac.jp

Multiple myeloma (MM) is a hematologic malignancy of human plasma cells, and myeloma cells can be classified into several subpopulations according to phenotypic differences, such as CD38 MPC-1- CD49e- immature, CD38 MPC-1+ CD49e- intermediate and CD38 MPC-1+ CD49e+ mature myeloma cells. The expression of the CD45 molecule on myeloma cells is quite variable, and the physiological consequence of CD45 on myeloma cells is still unknown. Recently, we have found that a few MPC-1- immature myeloma cells express CD45 antigens while most myeloma cells do not express the CD45. MPC-1- CD45+ CD49e- but not MPC-1- CD45- CD49e- immature cells contain proliferating cells in response to interleukin-6 (IL-6). IL-6 can also induce expression of CD45 on the MPC-1- CD45- subpopulation of immature myeloma cells. In addition, myeloma cell lines responding to IL-6 express CD45, whereas cell lines proliferating independent of IL-6 do not express CD45. In the U266 cell line, IL-6 leads to the induction of CD45 expression and cell proliferation, indicating that IL-6-induced effects are closely linked to CD45 expression. Thus, there is a heterogeneity in human myeloma cells, and among these subpopulations immature myeloma cells expressing the CD45 molecules appear to proliferate in response to IL-6. In this review we propose the involvement of CD45 in MM pathogenesis, and the possible implications of CD45 as both a phenotypic marker and a functional molecule is discussed.

Publication Types:
Review

PMID: 10975383 [PubMed - indexed for MEDLINE]

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14: Annu Rev Med. 2000;51:245-70.

Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty.

Ershler WB, Keller ET.

Institute for the Advanced Studies in Aging and Geriatric Medicine, Washington, DC 20006, USA. wershler@iasia.org

Interleukin-6 (IL-6) is a proinflammatory cytokine that is normally tightly regulated and expressed at low levels, except during infection, trauma, or other stress. Among several factors that down-regulate IL-6 gene expression are estrogen and testosterone. After menopause or andropause, IL-6 levels are elevated, even in the absence of infection, trauma, or stress. IL-6 is a potent mediator of inflammatory processes, and it has been proposed that the age-associated increase in IL-6 accounts for certain of the phenotypic changes of advanced age, particularly those that resemble chronic inflammatory disease [decreased lean body mass, osteopenia, low-grade anemia, decreased serum albumin and cholesterol, and increased inflammatory proteins such as C-reactive protein (CRP) and serum amyloid A]. Furthermore, the age-associated rise in IL-6 has been linked to lymphoproliferative disorders, multiple myeloma, osteoporosis, and Alzheimer's disease. This overview discusses the data relating IL-6 to age-associated diseases and to frailty. Like the syndrome of inappropriate antidiuretic hormone, it is possible that certain clinically important late-life changes are due to an inappropriate presence of IL-6.

Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 10774463 [PubMed - indexed for MEDLINE]

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15: J Neuroimmunol. 1999 Dec;100(1-2):124-39.

Interleukin-6 expression and regulation in astrocytes.

Van Wagoner NJ, Benveniste EN.

Department of Cell Biology, The University of Alabama at Birmingham, 35294-0005, USA.

The physiological function of interleukin-6 (IL-6) within the central nervous system (CNS) is complex; IL-6 exerts neurotrophic and neuroprotective effects, and yet can also function as a mediator of inflammation, demyelination, and astrogliosis, depending on the cellular context. In the normal brain, IL-6 levels remain low. However, elevated expression occurs in injury, infection, stroke, and inflammation. Given the diverse biological functions of IL-6 and its expression in numerous CNS conditions, it is critical to understand its regulation in the brain in order to control its expression and ultimately its effects. Accumulating data demonstrate that the predominant CNS source of IL-6 is the activated astrocyte. Furthermore, a wide range of factors have been demonstrated to be involved in IL-6 regulation by astrocytes. In this review, we summarize information concerning IL-6 regulation in astrocytes, focusing on the role of proinflammatory factors, neurotransmitters, and second messengers.

Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 10695723 [PubMed - indexed for MEDLINE]

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16: Int J Biochem Cell Biol. 1999 Oct;31(10):1221-36.

Role of nuclear factor of activated T cells (NFAT) in the expression of interleukin-5 and other cytokines involved in the regulation of hemopoetic cells.

De Boer ML, Mordvinov VA, Thomas MA, Sanderson CJ.

Department of Molecular Immunology, TVWT Institute for Child Health Research, Perth, WA, Australia.

NFAT (nuclear factor of activated T cells) is a transcription factor that plays a role in the regulation of various cytokines, including those involved in the regulation of hemopoetic cells such as granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-4 (IL4), interleukin-3 (IL3), interleukin-13 (IL13) and interleukin-5 (IL5). In this report we provide a summary of the various locations in the promoters of each of these cytokines where NFAT has been shown or suggested to bind, and at which sites NFAT has been shown to be involved in transcriptional regulation. We also provide experimental data to show that the binding of NFAT to the nucleotides GAA at positions -113 to -111 of the human IL5 promoter is associated with functional activity in human T cells.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 10582349 [PubMed - indexed for MEDLINE]

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17: J Interferon Cytokine Res. 1999 Jun;19(6):563-73.

The interleukin-10 signal transduction pathway and regulation of gene expression in mononuclear phagocytes.

Donnelly RP, Dickensheets H, Finbloom DS.

Division of Cytokine Biology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA. donnelly@cber.fda.gov

Interleukin-10 (IL-10) activates a diverse array of functional responses in mononuclear phagocytes. Functional IL-10 receptor (IL-10R) complexes are tetramers consisting of two IL-10R1 polypeptide chains and two IL-10R2 chains. Binding of IL-10 to the extracellular domain of IL-10R1 activates phosphorylation of the receptor-associated Janus tyrosine kinases, JAK1 and Tyk2. These kinases then phosphorylate specific tyrosine residues (Y446 and Y496) on the intracellular domain of the IL-10R1 chain. Once phosphorylated, these tyrosine residues (and their flanking peptide sequences) serve as temporary docking sites for the latent transcription factor, STAT3 (signal transducer and activator of transcription-3). STAT3 binds to these sites via its SH2 (Src homology 2) domain, and is, in turn, tyrosine-phosphorylated by the receptor-associated JAKs. It then homodimerizes and translocates to the nucleus where it binds with high affinity to STAT-binding elements (SBE) in the promoters of various IL-10-responsive genes. One of these genes, SOCS-3 (Suppressor of Cytokine Signaling-3) is a member of a newly identified family of genes that inhibit JAK/STAT-dependent signaling. Moreover, the ability of IL-10 to induce de novo synthesis of SOCS-3 in monocytes correlates with its ability to inhibit expression of many genes in these cells, including endotoxin-inducible cytokines such as tumor necrosis factor-alpha (TNF-alpha) and IL-1. Thus, the ability of IL-10 to inhibit gene expression in monocytes is associated with its ability to rapidly induce synthesis of SOCS-3.

Publication Types:
Review

PMID: 10433356 [PubMed - indexed for MEDLINE]

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18: J Interferon Cytokine Res. 1999 May;19(5):429-38.

Regulation of interleukin-8 gene expression.

Roebuck KA.

Department of Immunology/Microbiology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA. kroebuck@rush.edu

Interleukin-8 (IL-8), a member of the CXC chemokine family, is an important activator and chemoattractant for neutrophils and has been implicated in a variety of inflammatory diseases. IL-8 is secreted in a stimulus-specific manner by a wide variety of cell types and is regulated primarily at the level of gene transcription. Functional studies indicate that IL-8 transcriptional responses to proinflammatory mediators are rapid and require only 100 nucleotides of 5'-flanking DNA upstream of the TATA box. Within the IL-8 promoter sequence are DNA binding sites for the inducible transcription factors AP-1, NF-IL-6, and NF-kappaB. Transcription factors in these families bind the IL-8 promoter as dimers, and several distinct subunit combinations have been identified as important for IL-8 transcription. In addition, these factors can act in concert to synergistically activate the IL-8 promoter. AP-1 and NF-IL-6 physically interact with NF-kappaB, and functional cooperativity among the factors appears to be critical for optimal IL-8 promoter activity in different cell types. IL-8 transcription appears to be activated by a promoter recruitment mechanism where inducible transcription factor binding to the IL-8 promoter is required for binding of constitutively active TATA box-binding proteins and formation of a stable preinitiation complex. This review discusses the regulatory role these higher-order synergistic interactions play in IL-8 transcription and in generation of the stimulus-specific and cell type-specific patterns of IL-8 expression.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 10386854 [PubMed - indexed for MEDLINE]

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19: Annu Rev Immunol. 1999;17:19-49.

The multifaceted regulation of interleukin-15 expression and the role of this cytokine in NK cell differentiation and host response to intracellular pathogens.

Waldmann TA, Tagaya Y.

Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. tawald@helix.nih.gov

Interleukin-15 (IL-15) is a 14- to 15-kDa member of the 4 alpha-helix bundle family of cytokines. IL-15 expression is controlled at the levels of transcription, translation, and intracellular trafficking. In particular, IL-15 protein is posttranscriptionally regulated by multiple controlling elements that impede translation, including 12 upstream AUGs of the 5' UTR, 2 unusual signal peptides, and the C-terminus of the mature protein. IL-15 uses two distinct receptor and signaling pathways. In T and NK cells the IL-15 receptor includes IL-2/15R beta and gamma c subunits, which are shared with IL-2, and an IL-15-specific receptor subunit, IL-15R alpha. Mast cells respond to IL-15 with a receptor system that does not share elements with the IL-2 receptor but uses a novel 60- to 65-kDa IL-15RX subunit. In mast cells IL-15 signaling involves Jak2/STAT5 activation rather than the Jak1/Jak3 and STAT5/STAT3 system used in activated T cells. In addition to its other functional activities in immune and nonimmune cells, IL-15 plays a pivotal role in the development, survival, and function of NK cells. Abnormalities of IL-15 expression have been described in patients with rheumatoid arthritis or inflammatory bowel disease and in diseases associated with the retroviruses HIV and HTLV-I. New approaches directed toward IL-15, its receptor, or its signaling pathway may be of value in the therapy of these disorders.

Publication Types:
Review

PMID: 10358752 [PubMed - indexed for MEDLINE]

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20: Immunol Rev. 1998 Oct;165:287-300.

Molecular regulation of interleukin-2 expression by CD28 co-stimulation and anergy.

Powell JD, Ragheb JA, Kitagawa-Sakakida S, Schwartz RH.

Laboratory of Cellular and Molecular Immunology, National Institutes of Health, Bethesda, MD 20892-0420, USA.

The consequences of T-cell receptor engagement (signal 1) are profoundly affected by the presence or absence of co-stimulation (signal 2). T-cell receptor (TCR) stimulation in the absence of CD28-mediated co-stimulation not only results in little interleukin (IL)-2 production, but induces a long lasting hyporesponsive state known as T-cell clonal anergy. The addition of CD28 ligation to signal 1, on the other hand, results in the production of copious amounts of IL-2. Our laboratory has utilized CD4+ Th 1 clones in an effort to understand the molecular events resulting in enhanced IL-2 production by co-stimulation and the inhibition of IL-2 production in anergy. Our current studies have focused on defining the post-transcriptional effects of CD28-enhanced IL-2 production. The data suggest that a major component of CD28's ability to regulate IL-2 production occurs at the level of message stability and involves the 3'-untranslated region of the message. In terms of anergy, our recent studies support the notion that it is not the result of TCR engagement in the absence of co-stimulation, but rather signal 1 in the absence of IL-2 receptor signaling and proliferation. Furthermore, T-cell anergy appears to be an active negative state in which IL-2 production is inhibited both at the level of signal transduction and by cis-dominant repression at the level of the IL-2 promoter.

Publication Types:
Review

PMID: 9850868 [PubMed - indexed for MEDLINE]

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21: Eur Cytokine Netw. 1998 Sep;9(3 Suppl):97-101.

Dysregulation of interleukin-2 receptor beta and interleukin-2 receptor gamma expression during HIV infection.

David D, Bani L, Moreau JL, Treilhou MP, Demaison C, Sun K, Février M, Salvucci O, Cayota A, Nakarai T, Chouaïb S, de Montalembert M, Joussemet M, Sugamura K, Ritz J, Dupont B, Pialoux G, Thèze J.

Unité d'Immunogénétique Cellulaire, Département d'Immunologie, Institut Pasteur, Paris, France.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 9831196 [PubMed - indexed for MEDLINE]

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22: Eur Cytokine Netw. 1998 Sep;9(3 Suppl):54-64.

Positive and negative regulation of interleukin-12 gene expression.

Ma X, Riemann H, Gri G, Trinchieri G.

The Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104, USA.

Interleukin-12 (IL-12) is a pivotal cytokine representing the link between the cellular and humoral branches of an effective host immune defense apparatus. IL-12 is a heterodimer produced by phagocytic, B, dendritic, and possibly other accessory cells in both innate and adaptive immune responses. It is a key factor in the induction of T cell-dependent and independent activation of macrophages, generation of T helper type 1 (Th1) and cytotoxic T cells, suppression of IgG1 and IgE production, induction of organ-specific autoimmunity, and resistance to bacterial and parasitic infections [1]. IL-12 has a powerful anti-tumor and anti-metastatic activity against many murine tumors [2-5] as well as human tumors [6-17]. The genes encoding the two heterologous chains of IL-12, p40 and p35 are located on different human chromosomes. Together, p40 and p35 form the biologically active IL-12. Their expressions are highly coordinated during an effective immune response. However, under some pathological conditions, IL-12 is under- or overexpressed, resulting either in a lack of resistance to microbial infection and to uncontrolled tumor growth, or in destructive inflammation, respectively. A transient or irreversible dysregulation of IL-12 production may reflect a pathogen/tumor cell-induced disruption in the highly coordinated expression of p40 and p35. The understanding of the molecular mechanisms governing the expression of IL-12 p40 and p35 genes in the context of interactions between pathogens and the immune system is essential in efforts aimed at designing therapeutic strategies to treat infectious and malignant diseases.

Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 9831187 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

23: Rinsho Byori. 1998 Aug;46(8):821-8.

[Molecular mechanism of interleukin-8 gene expression]

[Article in Japanese]

Mukaida N, Murayama T.

Department of Molecular Pharmacology, Cancer Research Institute, Kanazawa University.

Evidence is accumulating that interleukin-8 (IL-8), discovered as a potent neutrophil chemotactic factor, plays a crucial role in establishing acute neutrophil-mediated inflammation by exerting various activities against non-leukocytic as well as leukocytic cells. Various types of cells can rapidly produce a large amount of IL-8 upon stimulation with inflammatory stimuli, such as lipopolysaccharide, IL-1, and tumor necrosis factor (TNF). However, IL-8 production is tightly regulated at several levels, particularly at the transcriptional levels to prevent aberrant production. Our previous experiments demonstrated that IL-8 gene transcription requires the cooperative activation of a transcription factor, NF-kappa B, with an additional transcription factor, AP-1 or NF-IL6, depending on types of cells and stimuli. In addition, we recently observed that infection with Helicobacter pylori or cytomegalovirus activated NF-kappa B, therapy inducing IL-8 protein secretion as well as IL-8 gene transcription. Moreover, IL-8, in turn, enhanced cytomegalovirus replication and infectious virion production. Collectively, these results suggest the potential involvement of IL-8 in the pathology of bacterial or viral infection.

Publication Types:
English Abstract
Review

PMID: 9760836 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

24: Leuk Lymphoma. 1998 Feb;28(5-6):443-50.

New directions in understanding interleukin-5 gene expression.

Schwenger GT, Sanderson CJ.

TVW Telethon Institute for Child Health Research, West Perth WA, Australia. gretchen@ichr.uwa.edu.au

Specific regulation of the interleukin-5 (IL-5) gene is implied by the unique control of eosinophilia which is regulated by IL-5. In studies of IL-5 gene expression, the only control elements identified for the IL-5 gene have been transcriptional elements in the 5' untranslated region (UTR). Significant differences exist in the arrangement of the murine and human IL-5 promoters, which is surprising considering the tight regulation of the gene. Novel palindromic regulatory elements involved in transcriptional regulation have been found in the 5' UTR and new results show the presence of transcriptional elements in the 3' UTR. Post-transcriptional control mechanisms in both the 5' and 3' UTRs have also been described.

Publication Types:
Review

PMID: 9613973 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

25: Int Rev Immunol. 1998;16(3-4):285-308.

Interleukin-7, a non-redundant potent cytokine whose over-expression massively perturbs B-lymphopoiesis.

Mertsching E, Meyer V, Linares J, Lombard-Platet S, Ceredig R.

U184 INSERM, LGME du CNRS, Faculte de Medecine, Strasbourg, France.

Interleukin-7, originally described as a factor controlling the survival of B-cell progenitors, has been shown by gene knock-out technology to be a non-redundant cytokine. Of all single cytokine knock-out mice, those in which the IL-7 gene has been ablated show a profound defect in lymphocyte development. Likewise, mice in which signals emanating from the corresponding receptor, whether it be by ablation of the unique alpha or common gamma chain of the receptor, or by interference with downstream signalling elements generated by this receptor complex, also show profound defects in lymphocyte differentiation. Transgenic mice over-expressing the IL-7 gene also show profound changes in lymphocyte development which, in some instances can result in the development of lymphoid tumours. Here, we review some of these aspects of IL-7 biology with particular reference to an IL-7 over-expressing transgenic mouse line in which the IL-7 transgene is controlled by the mouse MHC class II promoter.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 9505192 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

26: Curr Opin Immunol. 1997 Dec;9(6):776-81.

Genes that regulate interleukin-4 expression in T cells.

Szabo SJ, Glimcher LH, Ho IC.

Harvard School of Public Health, Department of Cancer Biology, Boston, MA 02115, USA. sjszabo@mbcrr.harvard.edu

Interleukin-4 is an immunomodulatory cytokine which plays a central role in the regulation of allergic and atopic immune responses. Significant progress has been made in gaining a detailed understanding of the transcriptional regulation of the interleukin-4 gene. The recent identification and characterization of several key transcription factors has helped to elucidate the molecular mechanisms of T helper cell cytokine gene expression.

Publication Types:
Review

PMID: 9492977 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

27: Kidney Int. 1997 Feb;51(2):419-25.

Hypoxia-induced modulation of endothelial cell properties: regulation of barrier function and expression of interleukin-6.

Yan SF, Ogawa S, Stern DM, Pinsky DJ.

Department of Physiology, Columbia University, College of Physicians and Surgeons, New York, New York, USA.

The endothelial cell response to hypoxia involves a range of adaptive mechanisms that reflect an active response of the cell's biosynthetic and metabolic apparatus. Hypoxia-mediated suppression of endothelial barrier function, resulting in increased vascular leakage, is likely to contribute to pulmonary and cerebral edema associated with high altitude and is closely associated with a fall in intracellular cyclic AMP levels. Buttressing of this second messenger pathway in the endothelium using membrane permeant cyclic AMP analogs prevents increased vascular leakage due to hypoxia. Application of this principle to organ preservation has shown that supplementation with cyclic AMP analogs or inhibition of endogenous cAMP metabolism enables extension of the time a harvested organ can remain extracorporeally, after which transplantation is successful. The underlying mechanism through which cyclic AMP exerts its effects appears to be maintenance of vascular homeostasis in the graft. A distinct adaptive mechanism triggered in the endothelium by hypoxia is expression of the cytokine interleukin-6 (IL-6) by a novel mechanism involving transcription driven by the nuclear factor IL-6 (NF-IL-6) DNA binding site in the promoter. IL-6 may exert protective effects on vascular function, thereby limiting vascular injury by a different mechanism than those recruited by elevated cAMP levels. These studies provide insights into tow independent mechanisms through which endothelium responds to oxygen deprivation, and suggest possible new approaches to attentuate vascular injury associated with ischemia.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 9027716 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

28: Adv Exp Med Biol. 1997;427:145-53.

Short chain fatty acids inhibit the expression of the neutrophil chemoattractant, interleukin 8, in the Caco-2 intestinal cell line.

Huang N, Wu GD.

Department of Internal Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.

Publication Types:
Review

PMID: 9361840 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

29: Endocrinology. 1996 Sep;137(9):4027-36.

Dual expression of p80 type I and p68 type II interleukin-I receptors on anterior pituitary cells synthesizing growth hormone.

French RA, Zachary JF, Dantzer R, Frawley LS, Chizzonite R, Parnet P, Kelley KW.

Department of Veterinary Pathobiology, University of Illinois, Urbana-Champaign 61801, USA.

Interleukin-1 alpha (IL-1 alpha) and IL-1 beta bind to either the p80 type I IL-1 receptor (IL-1RI) or the p68 type II IL-1R (IL-1RII) on both T and B lymphocytes. We and others have previously shown that the anterior pituitary gland also has specific high affinity binding sites for IL-1 alpha (Kd = approximately 1 nM) and expresses transcripts for both isoforms of the IL-1R. However, the identity of cells in the anterior pituitary gland that express the IL-1R and whether different populations of adenohypophyseal cells express different isoforms of the IL-1R remain unknown. Here we have used a combination of immunohistochemistry and histochemistry to localize IL-1RI and IL-1RII to specific target cells in the mouse anterior pituitary gland. Perfusion-fixed, paraffin-embedded sections of anterior pituitary gland were immunolabeled with well characterized monoclonal antibodies to either IL-1RI or IL-1RII and counterstained using a modified Gomori's method to document acidophils and basophils. Immunolabeling demonstrated that both IL-1RI and IL-1RII were abundantly expressed on a single population of anterior pituitary gland cells and that these cells could be classified on the basis of histochemical staining as a subpopulation of acidophils. The distribution, morphology, and proportion of cells immunolabeled for IL-1RI and IL-1RII were consistent with GH-synthesizing cells. To confirm this hypothesis, a modified indirect avidin-biotin complex, sequential peroxidase/alkaline phosphatase technique was used to label anterior pituitary gland cells with antibodies to IL-1RI followed by antibodies to IL-1RII, GH, PRL, or ACTH. The IL-1RI-positive cells predominately coexpressed IL-1RII and GH, but very little, if any, PRL or ACTH. These data establish that the predominant cell population in the murine anterior pituitary gland that constitutively expresses IL-1R stain as acidophils histochemically, is round to oval with dense granular cytoplasm and eccentric nuclei, synthesizes GH, and simultaneously expresses IL-1RI and IL-1RII isoforms.

Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 8756580 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

30: Mech Ageing Dev. 1996 Aug 29;89(3):125-54.

The effect of age on the expression of interleukin-2.

Pahlavani MA, Richardson A.

Geriatric Research Education and Clinical Center, Audie L. Murphy Memorial Veterans Hospital, San Antonio, Texas 78284, USA.

Interleukin-2 (IL-2) is a growth promoting cytokine that has received a great deal of attention over the past decade with respect to aging and cancer. It is produced primarily by helper T cells and regulates the growth and function of various cells that are involved in cellular and humoral immunity. The expression of IL-2 has been found to decrease with age in humans and rodents. The decline in IL-2 production has been shown to parallel the age-related decrease in immunologic function. Several studies indicate that treatment of lymphocytes from old subjects with exogenous IL-2 or infusion of IL-2 into old animals partially or completely restores some of the immune functions that decline with age. The age-related decline in IL-2 production has been shown to arise from a decline in IL-2 transcription, and a recent study suggests that the transcription factor NFAT (nuclear factor of activated T cells) may play a role in the decline in IL-2 transcription.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 8844635 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

31: Immunol Cell Biol. 1996 Apr;74(2):218-23.

How is expression of the interleukin-5 gene regulated?

Karlen S, Mordvinov VA, Sanderson CJ.

TVW Telethon Institute for Child Health Research, Perth, Australia.

Eosinophilia is a uniquely specific phenomenon regulated by interleukin-5 (IL-5), suggesting specific control for IL-5 expression. However in eosinophilia IL-5 is often co-expressed with other lymphokines such as IL-4, indicating that common, as well as independent, control mechanisms must exist. IL-5 gene expression is regulated at the transcriptional level. The molecular analysis of the IL-5 promoter region reveals the presence of positive regulatory sites that are common to many lymphokine genes. Results from immunosuppression studies suggest that the key control mechanism of IL-5 regulation may not depend on specific regulatory factors but on how gene expression is activated.

Publication Types:
Review

PMID: 8724013 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

32: Ann N Y Acad Sci. 1995 Jul 21;762:222-36; discussion 236-7.

Membrane-bound and soluble interleukin-6 receptor: studies on structure, regulation of expression, and signal transduction.

Heinrich PC, Graeve L, Rose-John S, Schneider-Mergener J, Dittrich E, Erren A, Gerhartz C, Hemann U, Lütticken C, Wegenka U, et al.

Institut für Biochemie, RWTH Aachen, Germany.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 7545364 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

33: Immunobiology. 1995 Jul;193(2-4):254-8.

The interplay between lymphoid-specific and ubiquitous transcription factors controls the expression of interleukin 2 gene in T lymphocytes.

Avots A, Escher C, Müller-Deubert S, Neumann M, Serfling E.

Institute of Pathology, University of Würzburg, Germany.

Publication Types:
Review

PMID: 8530151 [PubMed - indexed for MEDLINE]

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34: Stem Cells. 1995 Jul;13(4):324-35.

Regulation of granulocyte-macrophage colony-stimulating factor and interleukin 3 expression.

Nimer SD, Uchida H.

Laboratory of Molecular Aspects of Hematopoiesis, Sloan-Kettering Institute for Cancer Research, New York, New York 10021, USA.

Granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin 3 (IL-3) are multilineage acting hematopoietic growth factors which have overlapping but distinct biological properties. Cellular sources of IL-3 are confined to activated T cells, natural killer (NK) cells, mast cells and possibly megakaryocytes, while these cells and activated macrophages, fibroblasts and endothelial cells are important sources of GM-CSF. In vitro studies have implicated both cytokines in the autocrine growth of human myeloid or murine mast cell leukemias. The human GM-CSF and IL-3 genes map to the long arm of chromosome 5, show similar genomic structures, and share several conserved elements in their 5' and 3' flanking regions. The promoters of these genes contain a variety of positive and negative regulatory regions, and the level of expression of these genes is controlled by both transcriptional and post-transcriptional mechanisms.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 7549890 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

35: New Horiz. 1995 May;3(2):276-87.

Regulation of cytokine gene expression: tumor necrosis factor, interleukin-1, and the emerging biology of cytokine receptors.

Williams G, Giroir BP.

Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9063, USA.

Cytokines are bioactive molecules which mediate host responses to inflammatory stimuli. For cytokines to exert their effects, a number of molecular processes must occur. Inflammatory cells must sense the presence of a stimulus, often by detection of that stimulus via cell-surface receptors. Information detected at the cell surface must be transduced intracellularly, and the machinery of cytokine messenger RNA and protein synthesis initiated. Once secreted, cytokines must bind specific receptors on target tissues; these receptors in turn transduce signals which alter target cell phenotypes and responses. Each one of these steps is tightly regulated and may serve as a target for therapeutic manipulation. In this article, the regulation of cytokine gene expression is summarized, with particular emphasis on the regulation of tumor necrosis factor alpha and interleukin-1 biosynthesis. Attention is focused on therapeutic agents which alter cytokine production or activity, some of which are currently used in the ICU.

Publication Types:
Review

PMID: 7583169 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

36: Am J Respir Crit Care Med. 1994 Nov;150(5 Pt 2):S50-3.

Regulation of interleukin-5 and granulocyte-macrophage colony-stimulating factor expression.

Cousins DJ, Staynov DZ, Lee TH.

Department of Allergy and Allied Respiratory Disorders, U.M.D.S., Guy's Hospital, London, United Kingdom.

This review concerns the regulation of expression of the two main eosinophil differentiating factors, interleukin-5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF). The latter, GM-CSF, is expressed in a wide variety of differentiated and non-differentiated cell types: T cells, monocytes, macrophages, fibroblasts, and endothelial cells. On the other hand, IL-5 is only expressed by a limited number of fully differentiated cells: eosinophils, mast cells, and a subset of T cells. Activation of GM-CSF in T cells and non-T cells occurs by different mechanisms, regulated both transcriptionally and post-transcriptionally. The transcriptional activation of GM-CSF via protein kinase C pathway and via viral transactivating proteins involves different regulatory elements of its promoter. Although one of these cis acting elements is common to IL-5, the activation of IL-5 apparently proceeds via different mechanism(s).

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 7952592 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

37: Prog Neurobiol. 1994 Nov;44(4):397-432.

Gene expression and function of interleukin 1, interleukin 6 and tumor necrosis factor in the brain.

Schöbitz B, De Kloet ER, Holsboer F.

Max Plank Institute of Psychiatry, Department of Neuroendocrinology, Munich, Germany.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 7886232 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

38: Eur Cytokine Netw. 1994 Nov-Dec;5(6):573-92.

Interleukin-1: a gene expression system regulated at multiple levels.

Auron PE, Webb AC.

Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.

Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 7727690 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

39: J Allergy Clin Immunol. 1994 Sep;94(3 Pt 2):594-604.

Signals and nuclear factors that regulate the expression of interleukin-4 and interleukin-5 genes in helper T cells.

Lee HJ, Matsuda I, Naito Y, Yokota T, Arai N, Arai K.

Department of Molecular and Developmental Biology, University of Tokyo, Japan.

Mouse thymoma line EL-4 cells produce cytokines such as interleukin (IL)-2, IL-3, IL-4, IL-10, and granulocyte-macrophage colony-stimulating factor in response to phorbol 12-myristate 13-acetate (PMA). EL-4 cells also produce low levels of IL-5 when stimulated by PMA alone; however, cAMP greatly augments PMA-dependent IL-5 production. A transient transfection assay revealed that two signals, PMA and cAMP, are required for optimal activation of the IL-5 promoter. In contrast, cAMP almost completely inhibited the PMA-dependent activation of the endogenous IL-2 gene, as well as the transfected IL-2 promoter. These results indicate that the IL-5 gene is positively regulated by cAMP in a manner opposite to that for the IL-2 gene. One of the nuclear factors (NFs) that regulates the response of the IL-5 promoter to cAMP and PMA has properties similar to NF for activated t cell. The P sequence of the IL-4 gene, defined as a responsive element for PMA and calcium ionophore (A23187), shares sequence similarity with the NF kappa B and the NF-activated T cell binding sites. We attempted to determine whether NF(P), a nuclear factor specific for the P sequence, is related to NF-kappa B and nuclear factor for activated T cell (NF-AT). In electromobility shift assays both NF-kappa B (P65 or P65/P50 heterodimer) and NF-AT bound to the P sequence. However, sequence specificity of NF-AT was more similar to that of NF(P), and only a small amount of P65 was detected in NF(P). These results indicate that a component or components of NF-AT have the potential to reconstitute NF(P), whereas NF-kappa B alone does not account for NF(P) in Jurkat crude extract. Taken together, these results suggest that NF-AT-like factors are involved in the regulation of IL-4 and IL-5 genes.

Publication Types:
Review

PMID: 8083467 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

40: Allergy. 1994 Sep;49(8):576-86.

Role of interleukin-4 and interleukin-13 in synthesis of IgE and expression of CD23 by human B cells.

Punnonen J, Aversa G, Cocks BG, de Vries JE.

DNAX Research Institute, Human Immunology Department, Palo Alto, CA.

Publication Types:
Review

PMID: 7544548 [PubMed - indexed for MEDLINE]

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41: Behring Inst Mitt. 1993 Aug;(92):202-9.

Tumor necrosis factor and interleukin 1 induce expression of the glycolipid verotoxin receptor in human endothelial cells. Implications for the pathogenesis of the haemolytic uraemic syndrome.

Van de Kar NC, Monnens LA, Van Hinsbergh VW.

Gaubius Laboratory IVVO-TNO, Leiden, The Netherlands.

Activation of the endothelium by TNF or IL-1 results in altered haemostatic properties of and leukocyte binding to the endothelium. In haemolytic uraemic syndrome, the endothelium of the kidney and sometimes other tissues is severely damaged, presumably by a bacterial toxin, verotoxin (VT). In vitro studies have demonstrated that endothelial cells become sensitive to this toxin when they are exposed to TNF alpha or IL-1, inflammatory mediators which are produced by monocytes and mesangial cells and which may play a role in the kidney. In this report we demonstrate the influence of inflammatory mediators on the binding of VT to endothelial cells. Preincubation of human endothelial cells with TNF alpha for 24 h resulted in a ten- to hundred-fold increase of specific binding sites for 125I-VT-1. IL-1 and lymphotoxin (TNF beta) also markedly increased VT-1 binding. An exposure of only 6 h to TNF alpha was already enough to enhance the number of VT-1 binding sites on endothelial cells for at least 2 days. In order to demonstrate that the increases in VT binding was due to an increase in the functional VT receptor, glycolipid extracts of TNF alpha-treated cells were analyzed by thin layer chromatography. An increase of globotriaosylceramide (Gb3) was observed, suggesting that that preincubation of endothelial cells with TNF alpha leads to an increase in Gb3 synthesis in these cells. Inhibition of protein synthesis by cycloheximide prevented the increase in VT receptors induced by TNF alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication Types:
Review

PMID: 8250811 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

42: Kidney Int Suppl. 1993 Jan;39:S149-53.

Influence of hemodialysis on interleukin-6 production and gene expression by peripheral blood mononuclear cells.

Pertosa G, Gesualdo L, Tarantino EA, Ranieri E, Bottalico D, Schena FP.

Chair of Nephrology, Dialysis and Transplantation, University of Bari, Italy.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 8468918 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

43: Adv Exp Med Biol. 1993;351:87-97.

Molecular mechanism of interleukin-8 gene expression.

Okamoto S, Mukaida N, Yasumoto K, Horiguchi H, Matsushima K.

Department of Pharmacology, Kanazawa University, Japan.

Publication Types:
Review

PMID: 7942301 [PubMed - indexed for MEDLINE]

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44: Nippon Rinsho. 1992 Aug;50(8):1833-9.

[Function, molecular structure and gene expression of interleukin-11 (IL-11/AGIF)]

[Article in Japanese]

Kawashima I, Ohsumi J, Miyadai K, Takiguchi Y.

Interleukin-11 (IL-11) is a novel cytokine that was identified in a medium conditioned by the primate bone marrow-derived stromal cell line PU-34. It was originally identified as a growth factor for the IL-6-dependent plasmacytoma cell line T1165. Adipogenesis inhibitory factor (AGIF) was cloned from the human bone marrow-derived cell line KM-102. The AGIF cDNA sequence was revealed to be identical to that of the IL-11 cDNA. AGIF inhibits the process of adipogenesis of the bone marrow-derived preadipocyte cell line H-1/A. Other biological activities of IL-11/AGIF, megakaryocytopoiesis, stem-cell proliferation, hepatic acute phase responses and antigen-specific antibody responses are also summarized.

Publication Types:
English Abstract
Review

PMID: 1433976 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

45: Nippon Rinsho. 1992 Aug;50(8):1827-32.

[Function, molecular structure and gene expression regulation of interleukin-10 (IL-10)]

[Article in Japanese]

Nakahata T, Tsuji K.

Department of Pediatrics, Shinshu University School of Medicine.

Interleukin-10 has a variety of biological activities. Murine interleukin-10 inhibits cytokine production by Th2 cells in the presence of macrophages, enhances T cell proliferation, sustains the viability of B cells in vitro, induces class II MHC antigen expression on B cells, enhances mast cell proliferation in the presence of IL-3 and/or IL-4, and inhibits cytokine production by macrophages. Human interleukin-10 inhibits cytokine production by human T cells and reduces antigen-specific human T cell proliferation by downregulation of class II MHC antigen expression on monocytes. cDNA clones encoding murine and human interleukin-10 exhibit a strong homology to BCRFI in Epstein-Barr virus. BCRFI conserves only a part of interleukin-10 activities.

Publication Types:
English Abstract
Review

PMID: 1433975 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

46: Nippon Rinsho. 1992 Aug;50(8):1821-6.

[Function, molecular structure and gene expression regulation of interleukin 9 (IL-9)]

[Article in Japanese]

Sonoda Y.

Department of Hygiene, Kyoto Prefectural University of Medicine.

Interleukin-9 (IL-9)/P40 is a recently reported murine growth factor for helper T-cell clones. It is produced by ConA stimulated CD4+ T-cells or several T-cell lines such as TUC 2.15 derived from C57Bl/6 mouse. In the murine system, IL-9/P40 directly supported proliferation of mucosal type mast cells, and also induced erythroid burst formation, indirectly. On the other hand, human IL-9, which is a homologue to murine P40, was cloned from a cDNA library prepared with mRNA isolated from PHA-induced T-cell line (C5MJ2). Analysis of the sequence of cDNA revealed a striking similarity between murine and human IL-9/P40. Human IL-9 supported formation of a subpopulation of erythroid bursts that are responsive to IL-3. In this communication, identification, cloning of cDNA, and biological activities of murine and human IL-9/P40 are discussed.

Publication Types:
English Abstract
Research Support, Non-U.S. Gov't
Review

PMID: 1433974 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

47: Nippon Rinsho. 1992 Aug;50(8):1769-75.

[Function, molecular structure and gene expression of interleukin-1]

[Article in Japanese]

Kasahara T, Kuno K, Matsushima K.

Department of Medical Biology and Parasitology, Jichi Medical School.

Recent cloning of human and murine IL-1 receptor (IL-1R) has revealed that there are at least two type of IL-1R: type I IL-1R is detected on T cells and fibroblasts and consists of 552 AAs with a cytoplasmic domain of 213 AAs, while type II is detected on B cells and monocytic cell lines and consists of 398 AAs with a short stretch intracytoplasmic domain of 29 AAs. Extracytoplasmic portion of IL-1R has some homology with vaccinia virus B15 Ag or fibroblast protein ST-2, while cytoplasmic portion has considerable similarity with Drosophila toll gene. By transfecting murine type I IL-1R cDNA into a human Jurkat cell line, structural and functional potion required for the IL-1 signal transduction is determined. At least broad portion of cytoplasmic domain including 364-474 AAs from N-terminus are found to be essential, while PKC acceptor site (Ser-431 and Ser-509), and PKA acceptor site (Ser-528) are not essential for the IL-8 gene expression.

Publication Types:
English Abstract
Review

PMID: 1433966 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

48: Int J Immunopharmacol. 1992 Apr;14(3):401-11.

Review: transcriptional and post-transcriptional regulation of interleukin 1 gene expression.

Fenton MJ.

Department of Medicine, Boston University Medical Center, MA 02118.

Interleukin 1 alpha (IL-1 alpha) and beta (IL-1 beta) are proinflammatory cytokines that are encoded by distinct genes, but share most biological activities. During the past several years, intense investigation has focused on elucidating the molecular basis for the regulation of IL-1 alpha and beta gene expression. While the overall organization of both genes is conserved in mammals, the DNA sequence homology is surprisingly limited. This supports the growing body of evidence suggesting that each gene is regulated by distinct cis- and transacting elements. Most recently, novel regulatory DNA sequence elements and several nuclear regulatory proteins have been identified, which ultimately participate in the control of IL-1 beta gene transcription. In addition to transcriptional controls, the stability of IL-1 mRNA can be selectively regulated by various inducing stimuli and other cytokines. Taken together, these transcriptional and post-transcriptional regulatory mechanisms provide stringent, yet flexible, control over expression of the IL-1 alpha and beta genes.

Publication Types:
Review

PMID: 1618594 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

49: Ciba Found Symp. 1992;167:47-62; discussion 62-7.

Regulation of expression of the interleukin 6 gene: structure and function of the transcription factor NF-IL6.

Akira S, Isshiki H, Nakajima T, Kinoshita S, Nishio Y, Natsuka S, Kishimoto T.

Institute for Molecular and Cellular Biology, Osaka University, Japan.

The interleukin 6 (IL-6) promoter is rapidly and transiently activated by other cytokines, including IL-1 and tumour necrosis factor (TNF), as well as by phorbol esters and cyclic AMP agonists. Studies using promoter mutants suggested that an IL-1-responsive element mapped within the -180 to -123 region of the IL-6 promoter. A nuclear factor (NF-IL6) that recognized a unique sequence containing an inverted repeat, ACATTGCACAATCT, was identified within the region. Direct cloning of the human NF-IL6 revealed its similarity to C/EBP, a liver- and adipose tissue-specific transcription factor. C/EBP and NF-IL6 recognize the same nucleotide sequence, but exhibit distinct patterns of expression. NF-IL6 is expressed at a low level in normal tissues, but is rapidly and drastically induced by bacterial lipopolysaccharide (LPS) or inflammatory cytokines such as IL-1, TNF and IL-6. Recently, NF-IL6 has been shown to be identical to IL-6DBP, the DNA-binding protein which is responsible for IL-6-mediated induction of several acute-phase proteins. Evidence that NF-IL6 DNA-binding activity is increased after IL-6 stimulation without increased NF-IL6 protein synthesis demonstrates the importance of post-translational modification. There are some results indicating that phosphorylation is involved in transcriptional and binding activities of NF-IL6. Taken together, these findings indicate that NF-IL6 may be an important transcription factor on the signal transduction pathways of IL-1 and IL-6.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 1385054 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

50: Pol Arch Med Wewn. 1991 Oct;86(4):263-6.

[The role of expression of histocompatibility antigens class II (HLA-D) and interleukin-2 receptor in the process of rejection of transplanted organs]

[Article in Polish]

Nowaczyk M.

Zakładu Immunologii Instytutu Transplantologii AM w Warszawie.

Publication Types:
Review

PMID: 1813879 [PubMed - indexed for MEDLINE]

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51: J Cell Biochem. 1991 Apr;45(4):327-34.

Expression and function of interleukin-6 in epithelial cells.

Krueger J, Ray A, Tamm I, Sehgal PB.

Rockefeller University, New York, New York 10021.

Epithelial cells both produce and are affected by interleukin-6 (IL-6). Experiments with an adenocarcinoma-derived cell line (HeLa) reveal that activation of the transfected human IL-6 promoter occurs largely through two partially overlapping second messenger (cAMP, phorbol ester)- and cytokine (IL-1, TNF, serum)-responsive enhancer elements (MRE 1, -173 to -151 and MRE II, -158 to -145). MRE I contains the typical GACGTCA cAMP and phorbol ester-responsive (CRE-TRE) motif, whereas MRE II defines a new CRE/TRE motif that contains an imperfect dyad repeat. The mechanism of dexamethasone-mediated repression of IL-6 gene expression in epithelial cells involves occlusion of the entire MRE enhancer region and of the core-promoter elements (TATA-box and RNA start site) by ligand-activated glucocorticoid receptor. Enhanced levels of IL-6 expression are observed in many solid tumors and in the hyperproliferative (and glucocorticoid-suppressible) lesions of psoriasis. In cell culture, IL-6 enhances, inhibits, or has no effect on the proliferation of epithelial cells depending upon the cell-type examined. IL-6 enhances proliferation of keratinocytes but inhibits that of breast carcinoma cell lines ZR-75-1 and T-47D. In these breast carcinoma cells, IL-6 elicits a major change in cell phenotype which is characterized by a fibroblastoid morphology, enhanced motility, increased cell-cell separation, and decreased adherens type junctions (desmosomes and focal adhesions). The new data identify IL-6 as a regulator of epithelial cell growth and of cell-cell association.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 2045425 [PubMed - indexed for MEDLINE]

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52: Immunol Rev. 1991 Feb;119:95-103.

Fluorescence-based monitoring of interleukin-2 gene expression.

Emilie D, Matthes M, Grégoire C, Letourneur F, Wegener AM, Nicolas JF, Malissen B.

Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, France.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 1904398 [PubMed - indexed for MEDLINE]

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53: Adv Exp Med Biol. 1991;305:31-8.

Regulation of human interleukin 8 gene expression and binding of several other members of the intercrine family to receptors for interleukin-8.

Mukaida N, Hishinuma A, Zachariae CO, Oppenheim JJ, Matsushima K.

Cancer Treatment Division, National Cancer Institute, Frederick, Maryland 21702-1201.

IL-8 is produced by a wide variety of cells in response to polyclonal mitogens and cytokines. Northern blotting analysis revealed that IL-1, TNF and PMA could induce rapid expression of IL-8 mRNA in the absence of new protein synthesis. Nuclear run-off assays using different cell types demonstrated that IL-8 mRNA expression could at least be partly due to the activation of transcription. Cloning and determination of the entire sequence of IL-8 genomic DNA enabled us to explore the functional significance of the 5'-flanking enhancer region of the IL-8 gene by employing CAT assays. The results indicated that the region spanning from -94 to -71 bp is minimally sufficient for conferring responsiveness to IL-1, TNF and PMA. Further analysis using point-mutations revealed that this region consisted of two distinct cis-elements; one being the potential binding site for NFkB-like and the other for a C/EBP-like factor. These results suggested that all three stimuli, IL-1/TNF/PMA, modulate the identical combination of nuclear factors possibly by phosphorylation. We previously reported that these three stimuli activated the same serine protein kinase which phosphorylates identical 65 kDa and 74 kDa cytosol proteins in human PBMC. This IL-1/TNF/PMA-activated protein kinase is distinct from protein kinase A, protein kinase C or casein kinase in substrate specificity; in Ca and phospholipid dependency; in cyclic nucleotide dependency; and sensitivity to protein kinase inhibitors. Taken collectively, IL-1/TNF/PMA may activate a common serine protein kinase and this protein kinase may in turn directly or indirectly modulate several nuclear factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication Types:
Review

PMID: 1755377 [PubMed - indexed for MEDLINE]

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54: Adv Exp Med Biol. 1991;305:23-30.

Induction and regulation of interleukin-8 gene expression.

Strieter RM, Standiford T, Chensue SW, Kasahara K, Kunkel SL.

Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602.

Recent advances in understanding granulocyte elicitation have been made with the discovery and isolation of chemotactic cytokines. There is little doubt that these polypeptides will prove to be important mediators of disease process. Therefore, studies directed at understanding the production and regulation of interleukin-8 will continue to be a fertile area to explore mechanisms of disease processes and therapeutic targets.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 1755376 [PubMed - indexed for MEDLINE]

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55: Mol Biol Med. 1990 Apr;7(2):117-30.

Interleukin-6: a regulator of plasma protein gene expression in hepatic and non-hepatic tissues.

Sehgal PB.

Rockefeller University, New York, NY 10021.

The cytokine which is now called interleukin-6 (IL-6) has emerged as a major systemic alarm signal produced by essentially every injured tissue in response to almost every kind of damage. The hallmark of IL-6 gene regulation is its induction in many different tissues by inflammation-associated cytokines, bacterial products, virus infection and by activation of any of the three major signal transduction pathways (diacylglycerol, cAMP and Ca2(+)-activated). Many of these inducers act largely through a 23 base-pair "multi-response element" in the IL-6 promoter. Different tissues secrete multiple post-translationally modified forms of IL-6 (six protein species in the size range 23 to 30 kDa, and additional forms of size greater than or equal to 45 kDa). IL-6 plays a key role in activating a variety of host defence mechanisms that are aimed at limiting tissue injury. Thus, IL-6 elicits major changes in the biochemical, physiological and immunological status of the host (e.g. the "acute phase" plasma protein response). IL-6 enhances plasma protein gene expression not only in hepatocytes but also in monocytes, fibroblasts and lymphocytes. Elevated levels of IL-6 are observed in body fluids during acute and chronic infections, neoplasia and autoimmune diseases. The nature of the IL-6 receptor in hepatic and non-hepatic cells, the different signal transduction pathways involved in the regulation of particular liver genes by IL-6, the association between IL-6 levels in body fluids and clinical outcome and between IL-6 haplotypes and specific disease states remain to be explored in detail.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 2188060 [PubMed - indexed for MEDLINE]

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56: Pol Arch Med Wewn. 1989 Oct-Dec;82(4-6):190-4.

[The role of expression of histocompatibility antigens class II (HLA-D) and interleukin-2 receptor in the process of rejection of transplanted organs. I.]

[Article in Polish]

Nowaczyk M.

Zakładu Immunosupresji Doświadczalnej Instytutu Transplantologii AM w Warszawie.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 2518392 [PubMed - indexed for MEDLINE]

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57: Nutr Rev. 1989 Sep;47(9):285-7.

Interleukin-1 regulates zinc metabolism and metallothionein gene expression.

[No authors listed]

Publication Types:
Review

PMID: 2689938 [PubMed - indexed for MEDLINE]

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58: Year Immunol. 1989;5:126-59.

Interleukin-4: molecular structure and biochemical characteristics, biological function, and receptor expression.

Ohara J.

Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, Md.

Publication Types:
Review

PMID: 2652925 [PubMed - indexed for MEDLINE]

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59: Anticancer Res. 1987 Jul-Aug;7(4A):661-7.

Abnormal expression of interleukin-3 and leukaemia.

Hapel AJ, Young IG.

Department of Medicine and Clinical Science, Australian National University, Canberra.

Autonomous production of a required growth factor is one mechanism by which a cell may become tumorigenic. Several leukaemias have been described which secrete growth factors which may be involved in autocrine stimulation of cell proliferation. One of these leukaemias is WEHI-3B, a myelomonocytic leukaemia that constitutively produces interleukin-3 (IL-3). Cloning of the IL-3 gene has enabled us to investigate possible genetic changes in this gene in WEHI-3B cells which may have resulted in autonomous production of growth factor. We have shown that one of the IL-3 genes in WEHI-3B has been rearranged, as a result of the insertion of a 5.1 kilobase intracisternal A-type particle genome head to head with the 5' end of the IL-3 gene, 215 bases upstream of the IL-3 TATA box. The rearranged gene, when cloned into a lambda EMBL3A vector, could readily be expressed in COS-1 monkey cells, whereas the normal gene, in the same vector, was silent. Thus the insertion of the endogenous retroviral element has resulted in abnormal expression of the IL-3 gene and is postulated to have been a key genetic change in the development of this leukaemia. In an attempt to experimentally construct IL-3 producing leukaemias, IL-3 responsive FDC-P1 and 32D cl-23 cells were transfected with a retroviral expression vector containing the IL-3 gene. This resulted in autonomous production of IL-3 and continuous proliferation of the transfected cells. As a result of transfection, the FDC-P1 and 32D cl-23 cells became leukemogenic demonstrating the oncogenic potential of abnormal expression of IL-3. The autocrine nature of the experimental leukaemias was demonstrated by blocking their proliferation with an IL-3 neutralising antiserum. Similarly treated cultures of normal bone marrow cells also produced IL-3 and could be maintained for several months after transfection but were not leukemogenic. The factor-dependent cell lines are unable to differentiate in the presence of known CSF's and presumably have undergone other genetic changes which allow them to become leukemogenic when autocrine-stimulated. In contrast, the transfected bone marrow cells could differentiate and form colonies containing mature granulocytes and macrophages. The non-tumorigenic behaviour of the transfected bone marrow cells is consistent with the concept that several other genetic changes which effectively block differentiation are required for development of tumorigenicity in these cells.

Publication Types:
Review

PMID: 3310851 [PubMed - indexed for MEDLINE]

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60: Ann Intern Med. 1986 Oct;105(4):560-72.

The human interleukin-2 receptor: normal and abnormal expression in T cells and in leukemias induced by the human T-lymphotropic retroviruses.

Greene WC, Leonard WJ, Depper JM, Nelson DL, Waldmann TA.

The human receptor for interleukin-2 (T-cell growth factor) plays a critical role in the growth of T cells and is required for full expression of the normal immune response. Through hybridoma and recombinant DNA techniques, the interleukin-2 receptor protein has been biochemically characterized and purified; full-length copies of its complementary DNA have been molecularly cloned, sequenced, and expressed in eukaryotic cells; and the receptor gene has been characterized. Transient expression of the interleukin-2 receptor gene occurs during normal T-cell activation, and high- and low-affinity forms of the membrane receptor exist. A naturally occurring, soluble receptor has also been isolated, and its levels in serum correlate with the activity of various diseases. Deregulation of interleukin-2 receptor expression occurs in T-cell leukemias produced by the human T-lymphotropic retroviruses types I and II (HTLV-I and -II) and has been causally linked to the action of the trans-activator (taf) gene of these viruses. Monoclonal antibodies specific for the interleukin-2 receptor are being evaluated in the treatment of HTLV-I-induced leukemias and other conditions involving the inappropriate function of activated T cells.

Publication Types:
Review

PMID: 3019203 [PubMed - indexed for MEDLINE]

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61: Immunol Rev. 1986 Aug;92:81-101.

The murine interleukin-2 receptor: biochemical structure and regulation of expression.

Malek TR, Ashwell JD, Germain RN, Shevach EM, Miller J.

Publication Types:
Review

PMID: 3091485 [PubMed - indexed for MEDLINE]

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