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Resveratrol Inhibits Ionising Irradiation-Induced Inflammation in MSCs by Activating SIRT1 and Limiting NLRP-3 Inflammasome Activation
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
National Institute for Medical Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing 100088, China
* Authors to whom correspondence should be addressed.
Received: 3 May 2013; in revised form: 3 June 2013 / Accepted: 21 June 2013 / Published: 8 July 2013
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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MDPI and ACS Style
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.