Interleukin-6 and its receptor in autoimmunity.
Interleukin-6 (IL-6) is a multifunctional cytokine which acts on a wide variety of cells, regulating immune response, acute phase reaction and hematopoiesis. In accordance with its pleiotropic functions, IL-6 is indicated to be involved in the pathogenesis of several diseases including autoimmunities, lymphoid malignancies and inflammations. An elevated level of IL-6 is demonstrated in patients with rheumatoid arthritis and cardiac myxoma, which can explain symptoms of these diseases, such as autoantibody production and increase in acute phase proteins. Therefore, inhibitors of IL-6 production or IL-6 receptor-mediated signal transduction may be used for treatment of IL-6-related diseases. The IL-6 receptor system consists of two membrane proteins, a ligand-binding chain (IL-6R) and a non-ligand-binding signal transducer, gp130, both of which belong to the cytokine receptor family. Binding of IL-6 to IL-6R triggers the association of IL-6R and gp130, and gp130 in turn transduces the signal. A nuclear factor for controlling IL-6 gene expression (NF-IL6) is also involved in the transcriptional regulation of various acute-phase protein genes. IL-6-stimulation of hepatocytes, through modification of pre-existing NF-IL6 protein, leads to binding of NF-IL6 to IL-6-responsive elements and activation of acute-phase protein genes. NF-IL6 is shown to recognize the enhancer core sequence of several viruses, suggesting a possible relationship of virus infection and IL-6 expression.
Kishimoto
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Department of Medicine III, Osaka University Medical School, Japan.
D000209:Acute-Phase Proteins / Q000096:biosynthesis; D000595:Amino Acid Sequence; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology*; D019947:Receptors, Interleukin-6; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic / Q000276:immunology
D000209:Acute-Phase Proteins; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D009687:Nuclear Proteins; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D014157:Transcription Factors