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Interferon-α and interferon-γ differentially affect pancreatic β- cell phenotype and function

Abstract:

To better clarify individual roles of interferon (IFN)-α and IFNγ in β-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 β-cell lines. IFN-γ but not IFN-α decreased secreted and intracellular insulin concentrations in βTC6-F7 and βTC3 cells. Likewise, IFN-γ but not IFN-α treatment of β-cells upregulated mRNA expression of MHC class I(A) antigen- processing genes and surface expression of class I(A) molecules. Alternatively, class I(A) MHC expression was upregulated by IFN-γ and IFN- α in the P388D1 macrophage cell line. The observation of constitutive Ifn- α6 mRNA expression by a differentiated β-cell line substantiates previous indications that local expression of IFN-α in islets may trigger insulitis. Evidence that IFN-γ, a product of infiltrating leukocytes, directly decreases β-cell glucose sensitivity and increases MHC class I(A) cell surface expression supports the postulate that IFN-γ magnifies the insulitic process.