期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 14, 期 7, 页码 14105-14118出版社
MDPI
DOI: 10.3390/ijms140714105
关键词
radiation; IL-1 beta; SIRT1; NLRP3; resveratrol
资金
- Special Foundation of the Ministry of Health [201002009]
- National Natural Science Foundation of China [31170804, 31240052, 31200634]
- Natural Science Foundation of Tianjin [10JCZDJC16900, 11ZCGYSY02400, 12JCYBJC15300, 12JCYBJC32900]
- Science Research Foundation for Doctor-Subject of High School of the National Education Department [20101106110046, 20121106120044, 20121106120043]
- PUMC Youth Fund and Fundamental Research Funds for the Central Universities [2012G01, 2012J05]
- PUMC graduate student innovation fund
IL-1 beta, 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-1 beta, however, has remained elusive. The present study was designed to explore the potential effect of Sirt1 on IL-1 beta 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-1 beta mRNA and protein expression and that pretreatment with resveratrol, a Sirt1 activator, inhibited the radiation-induced IL-1 beta expression in a concentration-dependent manner, whereas the knockdown or inhibition of Sirt1 by nicotinamide significantly enhanced radiation-induced IL-1 beta expression. This effect can likely be attributed to Sirt1-mediated inhibition of NLRP-3 inflammasome activation because Sirt1 inhibits the transactivation potential of NF-kappa b 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-kappa b 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.
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