Study Title:

Resveratrol Regulates Primary Anti-Inflammatory Gene Switch, NF-kappB

Study Abstract

Objective: SIRT1, a class III histone/protein deacetylase, is known to interfere NF-kappaB signaling pathway and thereby has an anti-inflammatory function. Due to the central role of NF-kappaB in cytokine-mediated pancreatic beta-cell damage, we postulated that SIRT1 might work in pancreatic beta-cell damage model. Research Design and Methods: RINm5F (RIN) cells or isolated rat islets were treated with IL-1beta and IFN-gamma. SIRT1 was activated by resveratrol, a pharmacological activator, or ectopic overexpression. The underlying mechanisms of SIRT1 against cytokine toxicity were further explored. Results: Treatment of RIN cells with cytokines induced cell damage, and this damage was well correlated with the expression of inducible form of NO synthase (iNOS) and nitric oxide production. However, SIRT1 overexpression completely prevented cytokine-mediated cytotoxicity, as well as nitric oxide production and iNOS expression. The molecular mechanism by which SIRT1 inhibits iNOS gene expression appeared to involve the inhibition of NF-kappaB signaling pathway through deacetylation of p65. In addition, SIRT1 activation by either resveratrol or adenoviral-directed overexpression of SIRT1 could prevent cytokine toxicity and maintain normal insulin secreting responses to glucose in isolated rat islets. Conclusions: This study will provide valuable information not only into the mechanisms underlying beta-cell destruction but also into the regulation of SIRT1 as a possible target to attenuate cytokine-induced beta-cell damage.

Study Information

Lee JH, Song MY, Song EK, Kim EK, Sung Moon W, Han MK, Park JW, Kwon KB, Park BH
Overexpression of SIRT1 protects pancreatic {beta}-cells against cytokine toxicity through suppressing NF-{kappa}B signaling pathway.
2008 November

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