PMID- 31026586 OWN - NLM STAT- MEDLINE DCOM- 20200608 LR - 20200608 IS - 1873-4596 (Electronic) IS - 0891-5849 (Linking) VI - 137 DP - 2019 Jun TI - Hydrogen sulfide protects against DSS-induced colitis by inhibiting NLRP3 inflammasome. PG - 99-109 LID - S0891-5849(18)32424-9 [pii] LID - 10.1016/j.freeradbiomed.2019.04.025 [doi] AB - Hydrogen sulfide (H(2)S), 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 H(2)S exerts an anti-inflammatory effect on DSS-induced colitis by targeting NLRP3 inflammasome. Our data showed that DSS-induced colitis is attenuated by H(2)S, lessening the shortening of the colon lengths and colonic pathological damages. The cytokines TNF-alpha, IL-1beta, and IL-6 in colon samples were also significantly downregulated by H(2)S. Besides, H(2)S 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 H(2)S 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-1beta. Furthermore, the inhibitory effect of H(2)S 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 H(2)S exerts its protective effect on DSS-induced mouse colitis at least partly by inhibiting the activation of NLRP3 inflammasome pathway. CI - Copyright (c) 2019. Published by Elsevier Inc. FAU - Qin, Ming AU - Qin M AD - Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, 201203, China; State Key Laboratory of Quality Research in Chinese Medicine and School of Pharmacy, Macau University of Science and Technology, Macau, China; Department of Immunology, ZunYi Medical University, Zunyi, 563000, China. FAU - Long, Fen AU - Long F AD - Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, 201203, China. FAU - Wu, Weijun AU - Wu W AD - Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, 201203, China. FAU - Yang, Di AU - Yang D AD - Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, 201203, China. FAU - Huang, Mengwei AU - Huang M AD - Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, 201203, China. FAU - Xiao, Chenxi AU - Xiao C AD - Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, 201203, China. FAU - Chen, Xu AU - Chen X AD - School of Pharmacy, Guilin Medical University, China. FAU - Liu, Xinhua AU - Liu X AD - Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, 201203, China. Electronic address: liuxinhua@fudan.edu.cn. FAU - Zhu, Yi Zhun AU - Zhu YZ AD - Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, 201203, China; State Key Laboratory of Quality Research in Chinese Medicine and School of Pharmacy, Macau University of Science and Technology, Macau, China. Electronic address: yzzhu@must.edu.mo. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190423 PL - United States TA - Free Radic Biol Med JT - Free radical biology & medicine JID - 8709159 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Inflammasomes) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Reactive Oxygen Species) RN - 9042-14-2 (Dextran Sulfate) RN - EC 3.4.22.36 (Caspase 1) RN - EC 4.4.1.1 (Cystathionine gamma-Lyase) RN - YY9FVM7NSN (Hydrogen Sulfide) SB - IM MH - Animals MH - Anti-Inflammatory Agents/metabolism MH - Caspase 1/metabolism MH - Colitis/*metabolism MH - Colon/*pathology MH - Cystathionine gamma-Lyase/genetics/*metabolism MH - Dextran Sulfate MH - Disease Models, Animal MH - Humans MH - Hydrogen Sulfide/metabolism MH - Inflammasomes/metabolism MH - Inflammatory Bowel Diseases/*metabolism MH - Macrophages/*immunology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism MH - Reactive Oxygen Species/metabolism OTO - NOTNLM OT - Hydrogen sulfide OT - NADPH oxidase 4 OT - NLRP3 inflammasome OT - Nuclear factor erythroid 2-related factor 2 OT - Reactive oxygen species EDAT- 2019/04/27 06:00 MHDA- 2020/06/09 06:00 CRDT- 2019/04/27 06:00 PHST- 2018/11/17 00:00 [received] PHST- 2019/04/21 00:00 [revised] PHST- 2019/04/22 00:00 [accepted] PHST- 2019/04/27 06:00 [pubmed] PHST- 2020/06/09 06:00 [medline] PHST- 2019/04/27 06:00 [entrez] AID - S0891-5849(18)32424-9 [pii] AID - 10.1016/j.freeradbiomed.2019.04.025 [doi] PST - ppublish SO - Free Radic Biol Med. 2019 Jun;137:99-109. doi: 10.1016/j.freeradbiomed.2019.04.025. Epub 2019 Apr 23.