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.
Keywords: radiation; IL-1β; SIRT1; NLRP3; resveratrol
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Fu, Y.; Wang, Y.; Du, L.; Xu, C.; Cao, J.; Fan, T.; Liu, J.; Su, X.; Fan, S.; Liu, Q.; Fan, F. Resveratrol Inhibits Ionising Irradiation-Induced Inflammation in MSCs by Activating SIRT1 and Limiting NLRP-3 Inflammasome Activation. Int. J. Mol. Sci. 2013, 14, 14105-14118.
Fu Y, Wang Y, Du L, Xu C, Cao J, Fan T, Liu J, Su X, Fan S, Liu Q, Fan F. Resveratrol Inhibits Ionising Irradiation-Induced Inflammation in MSCs by Activating SIRT1 and Limiting NLRP-3 Inflammasome Activation. International Journal of Molecular Sciences. 2013; 14(7):14105-14118.
Fu, Yue; Wang, Yan; Du, Liqing; Xu, Chang; Cao, Jia; Fan, Tiqiang; Liu, Jianxiang; Su, Xu; Fan, Saijun; Liu, Qiang; Fan, Feiyue. 2013. "Resveratrol Inhibits Ionising Irradiation-Induced Inflammation in MSCs by Activating SIRT1 and Limiting NLRP-3 Inflammasome Activation." Int. J. Mol. Sci. 14, no. 7: 14105-14118.