Resveratrol inhibits interleukin 1β-mediated inducible nitric oxide synthase expression in articular chondrocytes by activating SIRT1 and thereby suppressing nuclear factor-κB activity

• Published in: European journal of pharmacology 2012-01, Vol.674 (2-3), p.73-79
• Main Authors: Lei, Ming, Wang, Ji-guo, Xiao, De-ming, Fan, Meng, Wang, Da-ping, Xiong, Jian-yi, Chen, Yang, Ding, Yue, Liu, Shang-li
• Format: Article
• Language: English
• Subjects: acetylation; Active Transport, Cell Nucleus - drug effects; Animals; Articular chondrocytes; Cell Nucleus - drug effects; Cell Nucleus - metabolism; chondrocytes; Chondrocytes - cytology; Chondrocytes - drug effects; Chondrocytes - enzymology; Chondrocytes - metabolism; DNA - metabolism; Gene Expression Regulation, Enzymologic - drug effects; Inducible nitric oxide synthase; inflammation; interleukin-1beta; Interleukin-1beta - pharmacology; Joints - cytology; nitric oxide; Nitric Oxide - biosynthesis; Nitric Oxide Synthase Type II - biosynthesis; Nitric Oxide Synthase Type II - metabolism; Nuclear factor-κB; osteoarthritis; Osteoarthritis - drug therapy; pharmacology; Rats; Rats, Wistar; Resveratrol; Signal Transduction - drug effects; SIRT1; Sirtuin 1 - metabolism; Stilbenes - pharmacology; Stilbenes - therapeutic use; transcription factor NF-kappa B; Transcription Factor RelA - antagonists & inhibitors; Transcription Factor RelA - genetics; Transcription Factor RelA - metabolism; transcriptional activation; Transcriptional Activation - drug effects
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2011.10.015

In chondrocytes, resveratrol, a natural SIRT1 activator, exerts an anti-inflammatory response via inhibition of nuclear factor kappaB (NF-κB). Given that SIRT1 inhibits the transactivation potential of NF-κB by deacetylating acetylated lysines in p65, the NF-κB subunit, we investigated the effects of resveratrol-activated SIRT1 on articular chondrocytes. We found that when chondrocytes were stimulated with interleukin 1β (IL-1β), the time- and dose-dependent expression of inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production was suppressed by resveratrol. Resveratrol-activated SIRT1 mediated this suppression. SIRT1 suppressed not only the nuclear translocation of NF-κB but also the acetylation of p65. Furthermore, acetylated Lys310 in p65, which must be present for transactivation activity, was the immediate downstream target of SIRT1. Therefore, SIRT1 protects against the inflammatory response induced by IL-1β in articular chondrocytes. Resveratrol, as an activator of SIRT1, merits consideration as a therapeutic agent in the treatment and prevention of osteoarthritis.