| Differential effects of proinflammatory cytokines on cell death and ER stress in insulin-secreting INS1E cells and the involvement of nitric oxide. | |
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MedLine Citation:
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PMID: 21531147 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Proinflammatory cytokines produced by immune cells destroy pancreatic beta cells in type 1 diabetes. The aim of this study was to investigate the cytokine network and its effects in insulin-secreting cells. INS1E cells were exposed to different combinations of proinflammatory cytokines. Cytokine toxicity was estimated by MTT assay and caspase activation measurements. The NFκB-iNOS pathway was analyzed by a SEAP reporter gene assay, Western-blotting and nitrite measurements. Gene expression analyses of ER stress markers, Chop and Bip, were performed by real-time RT-PCR. Cytokines tested in this study, namely IL-1β, TNFα and IFNγ, had deleterious effects on beta cell viability. The most potent toxicity exhibited IL-1β and its combinations with other cytokines. The toxic effects of IL-1β towards cell viability, caspase activation and iNOS activity were dependent on nitric oxide and abolished by an iNOS blocker. IL-1β was the strongest inducer of the NFκB activation. An iNOS blocker inhibited IL-1β-mediated NFκB activation in the first, initial phase of cytokine action, but did not affect significantly NFκB activation after prolonged incubation. Interestingly iNOS protein expression was induced predominantly by IL-1β and decreased in the presence of an iNOS blocker in the case of a short time exposure. The changes in the expression of ER stress markers were also almost exclusively dependent on the IL-1β presence and counteracted by iNOS blockade. Thus cytokine-induced beta cell death is primarily IL-1β mediated with a NO-independent enhancement by TNFα and IFNγ. The deleterious effects on cell viability and function are crucially dependent on IL-1β-induced nitric oxide formation. |
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Authors:
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Stella Kacheva; Sigurd Lenzen; Ewa Gurgul-Convey |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-4-28 |
Journal Detail:
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Title: Cytokine Volume: - ISSN: 1096-0023 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-5-2 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9005353 Medline TA: Cytokine Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier Ltd. All rights reserved. |
Affiliation:
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Institute of Clinical Biochemistry, Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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