title: Resveratrol inhibits ionising irradiation-induced inflammation in MSCs by activating SIRT1 and limiting NLRP-3 inflammasome activation.
abstract: IL-1β, a pro-inflammatory cytokine, has been shown to contribute to radiation injury. Sirt1, an NAD+-dependent class III protein deacetylase, plays an important role in the regulation of the proinflammatory cytokines involved in inflammation-associated diseases. The relationship between Sirt1 and IL-1β, however, has remained elusive. The present study was designed to explore the potential effect of Sirt1 on IL-1β expression induced by radiation and to provide a new target for the development of radiation protection drugs. Our results showed that radiation significantly increased IL-1β mRNA and protein expression and that pretreatment with resveratrol, a Sirt1 activator, inhibited the radiation-induced IL-1β expression in a concentration-dependent manner, whereas the knockdown or inhibition of Sirt1 by nicotinamide significantly enhanced radiation-induced IL-1β expression. This effect can likely be attributed to Sirt1-mediated inhibition of NLRP-3 inflammasome activation because Sirt1 inhibits the transactivation potential of NF-κb by deacetylation, which then suppresses NLRP3 transcription. Taken together, the results demonstrate that Sirt1 exerts anti-inflammatory effects by regulating NLRP3 expression partially through the NF-κb pathway in mesenchymal stem cells. More importantly, our findings suggest that resveratrol is an effective agent in protecting against radiation injury, and we provide a theoretical basis for developing a drug to protect against radiation injury by targeting Sirt1.
authors.affiliation: Tianjin Key Lab of Molecular Nuclear Medicine, Institute of Radiation Medicine of Chinese Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China. wddr0710@sina.com
authors.forename: Yue
authors.initials: Y
authors.lastname: Fu
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Liqing
authors.initials: L
authors.lastname: Du
authors.forename: Chang
authors.initials: C
authors.lastname: Xu
authors.forename: Jia
authors.initials: J
authors.lastname: Cao
authors.forename: Tiqiang
authors.initials: T
authors.lastname: Fan
authors.forename: Jianxiang
authors.initials: J
authors.lastname: Liu
authors.forename: Xu
authors.initials: X
authors.lastname: Su
authors.forename: Saijun
authors.initials: S
authors.lastname: Fan
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.forename: Feiyue
authors.initials: F
authors.lastname: Fan
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects; D016328:NF-kappa B / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009536:Niacinamide / Q000494:pharmacology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D011839:Radiation, Ionizing; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002352:Carrier Proteins; D053583:Interleukin-1beta; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D013267:Stilbenes; D009536:Niacinamide; D056564:Sirtuin 1; D000077185:Resveratrol