Negative regulation of inflammation by SIRT1.

Abstract

Sirtuin 1 (SIRT1), the mammalian Sir2 homologue, is a class III histone deacetylase shown to act on a wide range of histones and non-histone substrates. Numerous studies have demonstrated that SIRT1 regulates critical metabolic and physiological processes including senescence, stress resistance, metabolism and apoptosis. Recently, SIRT1 was also found to play an important role in modulating the development and progression of inflammation through deacetylating histones and critical transcription factor such as nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1), thus leading to transcriptional repression of various inflammation-related genes. There is increasing evidence that reduction of SIRT1 levels is closely correlated with many inflammatory diseases while pharmacologic activation of SIRT1 would be a promising therapeutic strategy for inflammation-related diseases.