期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 137, 期 -, 页码 99-109出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2019.04.025
关键词
Hydrogen sulfide; NLRP3 inflammasome; Reactive oxygen species; NADPH oxidase 4; Nuclear factor erythroid 2-related factor 2
资金
- National Natural Science Foundation of China [81673428, 81872861]
- Macau Science and Technology Development fund [FDCT 055/2016/A2, 033/2017/AMJ, 067/2018/A2]
- Zunyi Science & Technology Bureau in China [201805]
Hydrogen sulfide (H2S), as the third gasotransmitter, has been shown to be effective in the prevention of inflammation. In addition, the NLRP3 inflammasome is a key player in the pathogenesis of dextran sulfate sodium (DSS)-induced colitis. Therefore, the aim of our research was to determine whether H2S exerts an anti-inflammatory effect on DSS-induced colitis by targeting NLRP3 inflammasome. Our data showed that DSS-induced colitis is attenuated by H2S, lessening the shortening of the colon lengths and colonic pathological damages. The cytokines TNF-alpha, IL-1 beta, and IL-6 in colon samples were also significantly downregulated by H2S. Besides, H2S markedly suppressed the expression of NLRP3 and cleaved caspase-1 (p20) in colons from DSS-induced colitis mice. More importantly, CSE-/- mice were more susceptive to DSS-induced colitis when compared to wild-type (WT) mice. Our experimental results also suggested that H2S dose-dependently inhibits the activation of NLRP3 inflammasome in bone marrow-derived macrophages (BMDMs) by reducing the cleavage of caspase-1 and the secretion of IL-1 beta. Furthermore, the inhibitory effect of H2S is due to a reduction in reactive oxygen species (ROS) generation and partly dependent on the disruption of nuclear erythroid 2-related factor-2 (Nrf2) activation. Collectively, our study confirms that H2S exerts its protective effect on DSS-induced mouse colitis at least partly by inhibiting the activation of NLRP3 inflammasome pathway.
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