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Cytokine-induced human islet cell death in vitro correlateswith a persistently high phosphorylation of STAT-1, but not with NF-κB activation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
2012 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 418, no 4, 845-850 p.Article in journal (Refereed) Published
Abstract [en]

Studies of insulin producing β-cells have reported conflicting responses to NF-κB activation,encompassing both pro- and anti-apoptotic effects, possibly reflecting the use of β-cells fromdifferent species. Therefore, the aim of this study was to compare the temporal activation of NF-κB in rat and human insulin producing cells and relate this to the dynamics of cell death, STAT-1activation and the production of nitric oxide (NO). Rat RIN5AH and human islet cells wereexposed to the cytokines IL-1β and IFN-γ and the NOS inhibitor aminoguanidine. Cell death, NOproduction, ΙκΒα phosphorylation, p65 methylation, STAT-1 phosphorylation and cIAP-2 levelswere analyzed at different time-points. Cytokine-induced RIN5AH cell death occurred on day 1,and this was paralleled by NF-κB activation, STAT-1 phosphorylation and production of NO. Onthe other hand, the human islet cells instead died by an NO-independent mechanism on day 3and 5. This later occurring cell death was associated with a gradual decrease in ΙκΒα phosphorylation and p65 methylation, and a lowered expression of the NF-κB target genes ΙκΒα and cIAP-2. STAT-1 phosphorylation was persistently high during the entire cytokine exposureperiod in human islet cells. The results favor a pro-survival role of NF-κB and a pro-apoptoticrole of STAT-1 in human islet cells. Thus, rodent insulin producing cells may not be suitable asmodels for human β-cells in the context of cytokine-induced damage.

Place, publisher, year, edition, pages
2012. Vol. 418, no 4, 845-850 p.
Keyword [en]
Human islets, Apoptosis, NF-kappa B, STAT-1, Cytokines, Nitric oxide
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-167882DOI: 10.1016/j.bbrc.2012.01.130ISI: 000301332100045OAI: oai:DiVA.org:uu-167882DiVA: diva2:488701
Available from: 2012-02-02 Created: 2012-02-02 Last updated: 2017-12-08Bibliographically approved

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Hindlycke, HenriettaWelsh, Nils
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