Author:
Ma Zhen-Rong,Li Zhuo-Lin,Zhang Ni,Lu Bin,Li Xuan-Wu,Huang Ye-Hong,Nouhoum Dibo,Liu Xian-Shu,Xiao Ke-Chun,Cai Li-Ting,Xu Shao-Rui,Yang Xue-Xian O.,Huang Shuai-Qin,Wu Xiang
Abstract
Abstract
Background
Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is increasing worldwide. Although there is currently no completely curative treatment, helminthic therapy shows certain therapeutic potential for UC. Many studies have found that Trichinella spiralis (T.s) has a protective effect on UC, but the specific mechanism is still unclear.
Methods
Balb/c mice drank dextran sulfate sodium (DSS) to induce acute colitis and then were treated with T.s. In vitro experiments, the LPS combination with ATP was used to induce the pyroptosis model, followed by intervention with crude protein from T.s (T.s cp). Additionally, the pyroptosis agonist of NSC or the pyroptosis inhibitor vx-765 was added to intervene to explore the role of pyroptosis in DSS-induced acute colitis. The degree of pyroptosis was evaluated by western blot, qPCR and IHC, etc., in vivo and in vitro.
Results
T.s intervention significantly inhibited NLRP3 inflammasome activation and GSDMD-mediated pyroptosis by downregulating the expression of pyroptosis-related signatures in vitro (cellular inflammatory model) and in vivo (DSS-induced UC mice model). Furthermore, blockade of GSDMD-mediated pyroptosis by the caspase-1 inhibitor vx-765 has a similar therapeutic effect on DSS-induced UC mice with T.s intervention, thus indicating that T.s intervention alleviated DSS-induced UC in mice by inhibiting GSDMD-mediated pyroptosis.
Conclusion
This study showed that T.s could alleviate the pathological severity UC via GSDMD-mediated pyroptosis, and it provides new insight into the mechanistic study and application of helminths in treating colitis.
Graphical Abstract
Funder
National Natural Science Foundation of China
National Natural Sciences Foundation of China
National Key Research and Development Program of China
Publisher
Springer Science and Business Media LLC
Subject
Infectious Diseases,Parasitology,General Veterinary
Reference59 articles.
1. de Souza HSP, Fiocchi C, Iliopoulos D. The ibd interactome: an integrated view of aetiology, pathogenesis and therapy. Nat Rev Gastroenterol Hepatol. 2017;14:739–49.
2. Ulcerative colitis. Nat Rev Dis Primers. 2020. 6(1):73.
3. Shivashankar R, Tremaine WJ, Harmsen WS, Loftus EV Jr. Incidence and prevalence of crohn’s disease and ulcerative colitis in olmsted county, minnesota from 1970 through 2010. Clin Gastroenterol Hepatol. 2017;15:857–63.
4. Jie F, Xiao S, Qiao Y, You Y, Feng Y, Long Y, et al. Kuijieling decoction suppresses nlrp3-mediated pyroptosis to alleviate inflammation and experimental colitis in vivo and in vitro. J Ethnopharmacol. 2021;264:113243.
5. Bergsbaken T, Fink SL, Cookson BT. Pyroptosis: host cell death and inflammation. Nat Rev Microbiol. 2009;7:99–109.
Cited by
6 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献