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-α, IL-1β, 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-1β. 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.
Keywords: Hydrogen sulfide; NADPH oxidase 4; NLRP3 inflammasome; Nuclear factor erythroid 2-related factor 2; Reactive oxygen species.
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