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• W1989478714 endingPage "e17" @default.
• W1989478714 startingPage "e17" @default.
• W1989478714 abstract "There are at least two phases of beta-cell death during the development of autoimmune diabetes: an initiation event that results in the release of beta-cell-specific antigens, and a second, antigen-driven event in which beta-cell death is mediated by the actions of T lymphocytes. In this report, the mechanisms by which the macrophage-derived cytokine interleukin (IL)-1 induces beta-cell death are examined. IL-1, known to inhibit glucose-induced insulin secretion by stimulating inducible nitric oxide synthase expression and increased production of nitric oxide by beta-cells, also induces beta-cell death.To ascertain the mechanisms of cell death, the effects of IL-1 and known activators of apoptosis on beta-cell viability were examined. While IL-1 stimulates beta-cell DNA damage, this cytokine fails to activate caspase-3 or to induce phosphatidylserine (PS) externalization; however, apoptosis inducers activate caspase-3 and the externalization of PS on beta-cells. In contrast, IL-1 stimulates the release of the immunological adjuvant high mobility group box 1 protein (HMGB1; a biochemical maker of necrosis) in a nitric oxide-dependent manner, while apoptosis inducers fail to stimulate HMGB1 release. The release of HMGB1 by beta-cells treated with IL-1 is not sensitive to caspase-3 inhibition, while inhibition of this caspase attenuates beta-cell death in response to known inducers of apoptosis.These findings indicate that IL-1 induces beta-cell necrosis and support the hypothesis that macrophage-derived cytokines may participate in the initial stages of diabetes development by inducing beta-cell death by a mechanism that promotes antigen release (necrosis) and islet inflammation (HMGB1 release)." @default.
• W1989478714 created "2016-06-24" @default.
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• W1989478714 creator A5042963980 @default.
• W1989478714 creator A5051917442 @default.
• W1989478714 date "2005-12-20" @default.
• W1989478714 modified "2023-09-26" @default.
• W1989478714 title "Interleukin-1 Stimulates β-Cell Necrosis and Release of the Immunological Adjuvant HMGB1" @default.
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• W1989478714 doi "https://doi.org/10.1371/journal.pmed.0030017" @default.
• W1989478714 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1316065" @default.
• W1989478714 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16354107" @default.
• W1989478714 hasPublicationYear "2005" @default.
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