Interferon-alpha and interferon-gamma differentially affect pancreatic beta-cell phenotype and function.
To better clarify individual roles of interferon (IFN)-alpha and IFN-gamma in beta-cell pathology during the onset of type 1 diabetes mellitus, we compared the effects of these cytokines on insulin production and major histocompatibility complex (MHC) gene expression in pancreatic beta-cell lines. IFN-gamma but not IFN-alpha decreased secreted and intracellular insulin concentrations in betaTC6-F7 and betaTC3 cells. Likewise, IFN-gamma but not IFN-alpha treatment of beta-cells upregulated mRNA expression of MHC class IA antigen-processing genes and surface expression of class IA molecules. Alternatively, class IA MHC expression was upregulated by IFN-gamma and IFN-alpha in the P388D1 macrophage cell line. The observation of constitutive Ifn-alpha6 mRNA expression by a differentiated beta-cell line substantiates previous indications that local expression of IFN-alpha in islets may trigger insulitis. Evidence that IFN-gamma, a product of infiltrating leukocytes, directly decreases beta-cell glucose sensitivity and increases MHC class IA cell surface expression supports the postulate that IFN-gamma magnifies the insulitic process.
Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
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Baldeón
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Chun
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Gaskins
D000236:Adenoma; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D017931:DNA Primers; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000503:physiopathology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D007328:Insulin / Q000096:biosynthesis* / Q000235:genetics; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D008822:Mice, Transgenic; D010190:Pancreatic Neoplasms; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D011994:Recombinant Proteins; D014162:Transfection
D017931:DNA Primers; D015395:Histocompatibility Antigens Class I; D007328:Insulin; D007370:Interferon Type I; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D007371:Interferon-gamma