Inhibition of GSDMD-mediated pyroptosis triggered by Trichinella spiralis intervention contributes to the alleviation of DSS-induced ulcerative colitis in mice
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 Trichin...
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| Format: | Article |
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BMC
2023-08-01
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| Series: | Parasites & Vectors |
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| Online Access: | https://doi.org/10.1186/s13071-023-05857-3 |
| _version_ | 1797453757778231296 |
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| author | Zhen-Rong Ma Zhuo-Lin Li Ni Zhang Bin Lu Xuan-Wu Li Ye-Hong Huang Dibo Nouhoum Xian-Shu Liu Ke-Chun Xiao Li-Ting Cai Shao-Rui Xu Xue-Xian O. Yang Shuai-Qin Huang Xiang Wu |
| author_facet | Zhen-Rong Ma Zhuo-Lin Li Ni Zhang Bin Lu Xuan-Wu Li Ye-Hong Huang Dibo Nouhoum Xian-Shu Liu Ke-Chun Xiao Li-Ting Cai Shao-Rui Xu Xue-Xian O. Yang Shuai-Qin Huang Xiang Wu |
| author_sort | Zhen-Rong Ma |
| collection | DOAJ |
| description | 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 |
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| institution | Directory Open Access Journal |
| issn | 1756-3305 |
| language | English |
| last_indexed | 2024-03-09T15:26:33Z |
| publishDate | 2023-08-01 |
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| spelling | doaj.art-a6f32be1961143acb756e4c74e83ad2e2023-11-26T12:29:26ZengBMCParasites & Vectors1756-33052023-08-0116111210.1186/s13071-023-05857-3Inhibition of GSDMD-mediated pyroptosis triggered by Trichinella spiralis intervention contributes to the alleviation of DSS-induced ulcerative colitis in miceZhen-Rong Ma0Zhuo-Lin Li1Ni Zhang2Bin Lu3Xuan-Wu Li4Ye-Hong Huang5Dibo Nouhoum6Xian-Shu Liu7Ke-Chun Xiao8Li-Ting Cai9Shao-Rui Xu10Xue-Xian O. Yang11Shuai-Qin Huang12Xiang Wu13Department of Medical Parasitology, Xiangya School of Basic Medicine, Central South UniversityDepartment of Medical Parasitology, Xiangya School of Basic Medicine, Central South UniversityDepartment of Medical Parasitology, Xiangya School of Basic Medicine, Central South UniversityDepartment of Medical Parasitology, Xiangya School of Basic Medicine, Central South UniversityDepartment of Medical Parasitology, Xiangya School of Basic Medicine, Central South UniversityDepartment of Medical Parasitology, Xiangya School of Basic Medicine, Central South UniversityDepartment of Medical Parasitology, Xiangya School of Basic Medicine, Central South UniversityDepartment of Medical Parasitology, Xiangya School of Basic Medicine, Central South UniversityDepartment of Medical Parasitology, Xiangya School of Basic Medicine, Central South UniversityDepartment of Medical Parasitology, Xiangya School of Basic Medicine, Central South UniversityDepartment of Medical Parasitology, Xiangya School of Basic Medicine, Central South UniversityDepartment of Molecular & Genetic and Microbiology, University of New Mexico School of MedicineDepartment of Medical Parasitology, Xiangya School of Basic Medicine, Central South UniversityDepartment of Medical Parasitology, Xiangya School of Basic Medicine, Central South UniversityAbstract 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 Abstracthttps://doi.org/10.1186/s13071-023-05857-3Trichinella spiralisProtective effectUlcerative colitisInhibitionGSDMD-mediated pyroptosis |
| spellingShingle | Zhen-Rong Ma Zhuo-Lin Li Ni Zhang Bin Lu Xuan-Wu Li Ye-Hong Huang Dibo Nouhoum Xian-Shu Liu Ke-Chun Xiao Li-Ting Cai Shao-Rui Xu Xue-Xian O. Yang Shuai-Qin Huang Xiang Wu Inhibition of GSDMD-mediated pyroptosis triggered by Trichinella spiralis intervention contributes to the alleviation of DSS-induced ulcerative colitis in mice Parasites & Vectors Trichinella spiralis Protective effect Ulcerative colitis Inhibition GSDMD-mediated pyroptosis |
| title | Inhibition of GSDMD-mediated pyroptosis triggered by Trichinella spiralis intervention contributes to the alleviation of DSS-induced ulcerative colitis in mice |
| title_full | Inhibition of GSDMD-mediated pyroptosis triggered by Trichinella spiralis intervention contributes to the alleviation of DSS-induced ulcerative colitis in mice |
| title_fullStr | Inhibition of GSDMD-mediated pyroptosis triggered by Trichinella spiralis intervention contributes to the alleviation of DSS-induced ulcerative colitis in mice |
| title_full_unstemmed | Inhibition of GSDMD-mediated pyroptosis triggered by Trichinella spiralis intervention contributes to the alleviation of DSS-induced ulcerative colitis in mice |
| title_short | Inhibition of GSDMD-mediated pyroptosis triggered by Trichinella spiralis intervention contributes to the alleviation of DSS-induced ulcerative colitis in mice |
| title_sort | inhibition of gsdmd mediated pyroptosis triggered by trichinella spiralis intervention contributes to the alleviation of dss induced ulcerative colitis in mice |
| topic | Trichinella spiralis Protective effect Ulcerative colitis Inhibition GSDMD-mediated pyroptosis |
| url | https://doi.org/10.1186/s13071-023-05857-3 |
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