title: Resveratrol inhibits interleukin 1β-mediated inducible nitric oxide synthase expression in articular chondrocytes by activating SIRT1 and thereby suppressing nuclear factor-κB activity.
abstract: 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.
authors: Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No.107, Yanjiang West Road, 510120, Guangzhou, Guangdong Province, People's Republic of China.
authors: Ming
authors: M
authors: Lei
authors: Ji-guo
authors: JG
authors: Wang
authors: De-ming
authors: DM
authors: Xiao
authors: Meng
authors: M
authors: Fan
authors: Da-ping
authors: DP
authors: Wang
authors: Jian-yi
authors: JY
authors: Xiong
authors: Yang
authors: Y
authors: Chen
authors: Yue
authors: Y
authors: Ding
authors: Shang-li
authors: SL
authors: Liu
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D053583:Interleukin-1beta / Q000494:pharmacology*; D007596:Joints / Q000166:cytology; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis* / Q000378:metabolism; D010003:Osteoarthritis / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D053583:Interleukin-1beta; C498145:Rela protein, rat; D013267:Stilbenes; D051996:Transcription Factor RelA; D009569:Nitric Oxide; D004247:DNA; D052247:Nitric Oxide Synthase Type II; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D000077185:Resveratrol