Microcystin-LR Induces and Aggravates Colitis through NLRP3 Inflammasome-Mediated Pyroptosis in Mice
Inflammatory bowel disease (IBD) is a chronic, lifelong gastrointestinal disease, characterized by periods of activity and remission. The etiology of IBD is closely related to environmental factors. Previous studies have shown that the cyanotoxin microcystin-LR (MC-LR) causes intestinal damage, even...
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| Format: | Article |
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MDPI AG
2023-07-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/15/7/447 |
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| author | Yue Yang Pan Gong Xiuyan Long Yuanjuan Jiang Mingmei Ye Sifan Tao Yahui Su Fei Yang Li Tian |
| author_facet | Yue Yang Pan Gong Xiuyan Long Yuanjuan Jiang Mingmei Ye Sifan Tao Yahui Su Fei Yang Li Tian |
| author_sort | Yue Yang |
| collection | DOAJ |
| description | Inflammatory bowel disease (IBD) is a chronic, lifelong gastrointestinal disease, characterized by periods of activity and remission. The etiology of IBD is closely related to environmental factors. Previous studies have shown that the cyanotoxin microcystin-LR (MC-LR) causes intestinal damage, even IBD. To explore MC-LR’s effects and potential mechanisms on IBD occurrence and development, we used dextran-sulfate sodium gavage (DSS) and MC-LR together for the first time in mice. There were four groups of mice: (A) mice given PBS gavage (control, CT); (B) mice given 3% DSS gavage (DSS); (C) mice given 200 µg/kg MC-LR gavage (MC-LR); and (D) mice given 3% DSS + 200 µg/kg MC-LR gavage (DSS + MC-LR). Compared with the CT group, the MC-LR group and the DSS group demonstrated more severe colitis results, which presented as higher weight loss, an increased Disease Activity Index (DAI) score, shorter colon length, a higher degree of tissue structural damage, more apoptotic cells, and greater pro-inflammatory cytokines. Similarly, the DSS + MC-LR group showed more severe colitis compared with the DSS group. Subsequent experiments confirmed that MC-LR or DSS increased the expression of pyroptosis-related proteins mediated by the nucleotide-binding domain-like receptor protein 3 (NLRP3). Likewise, compared with the DSS group, the DSS + MC-LR group expressed these proteins at a higher level. In conclusion, our research is the first to show that MC-LR may induce colitis, and even IBD, through NLRP3 inflammasome-mediated pyroptosis, and it could aggravate DSS-induced colitis in the same way. |
| first_indexed | 2024-03-11T00:35:32Z |
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| spelling | doaj.art-c4f34b1dae2e4833af66f3091ddc74772023-11-18T21:38:20ZengMDPI AGToxins2072-66512023-07-0115744710.3390/toxins15070447Microcystin-LR Induces and Aggravates Colitis through NLRP3 Inflammasome-Mediated Pyroptosis in MiceYue Yang0Pan Gong1Xiuyan Long2Yuanjuan Jiang3Mingmei Ye4Sifan Tao5Yahui Su6Fei Yang7Li Tian8Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410078, ChinaDepartment of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410078, ChinaDepartment of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410078, ChinaHunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, University of South China, Hengyang 421001, ChinaDepartment of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410078, ChinaDepartment of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410078, ChinaXiangya School of Medicine, Central South University, 172 Tongzipo Road, Changsha 410078, ChinaHunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, University of South China, Hengyang 421001, ChinaDepartment of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410078, ChinaInflammatory bowel disease (IBD) is a chronic, lifelong gastrointestinal disease, characterized by periods of activity and remission. The etiology of IBD is closely related to environmental factors. Previous studies have shown that the cyanotoxin microcystin-LR (MC-LR) causes intestinal damage, even IBD. To explore MC-LR’s effects and potential mechanisms on IBD occurrence and development, we used dextran-sulfate sodium gavage (DSS) and MC-LR together for the first time in mice. There were four groups of mice: (A) mice given PBS gavage (control, CT); (B) mice given 3% DSS gavage (DSS); (C) mice given 200 µg/kg MC-LR gavage (MC-LR); and (D) mice given 3% DSS + 200 µg/kg MC-LR gavage (DSS + MC-LR). Compared with the CT group, the MC-LR group and the DSS group demonstrated more severe colitis results, which presented as higher weight loss, an increased Disease Activity Index (DAI) score, shorter colon length, a higher degree of tissue structural damage, more apoptotic cells, and greater pro-inflammatory cytokines. Similarly, the DSS + MC-LR group showed more severe colitis compared with the DSS group. Subsequent experiments confirmed that MC-LR or DSS increased the expression of pyroptosis-related proteins mediated by the nucleotide-binding domain-like receptor protein 3 (NLRP3). Likewise, compared with the DSS group, the DSS + MC-LR group expressed these proteins at a higher level. In conclusion, our research is the first to show that MC-LR may induce colitis, and even IBD, through NLRP3 inflammasome-mediated pyroptosis, and it could aggravate DSS-induced colitis in the same way.https://www.mdpi.com/2072-6651/15/7/447microcystin-LRinflammatory bowel diseaseNLRP3 inflammasomepyroptosis |
| spellingShingle | Yue Yang Pan Gong Xiuyan Long Yuanjuan Jiang Mingmei Ye Sifan Tao Yahui Su Fei Yang Li Tian Microcystin-LR Induces and Aggravates Colitis through NLRP3 Inflammasome-Mediated Pyroptosis in Mice Toxins microcystin-LR inflammatory bowel disease NLRP3 inflammasome pyroptosis |
| title | Microcystin-LR Induces and Aggravates Colitis through NLRP3 Inflammasome-Mediated Pyroptosis in Mice |
| title_full | Microcystin-LR Induces and Aggravates Colitis through NLRP3 Inflammasome-Mediated Pyroptosis in Mice |
| title_fullStr | Microcystin-LR Induces and Aggravates Colitis through NLRP3 Inflammasome-Mediated Pyroptosis in Mice |
| title_full_unstemmed | Microcystin-LR Induces and Aggravates Colitis through NLRP3 Inflammasome-Mediated Pyroptosis in Mice |
| title_short | Microcystin-LR Induces and Aggravates Colitis through NLRP3 Inflammasome-Mediated Pyroptosis in Mice |
| title_sort | microcystin lr induces and aggravates colitis through nlrp3 inflammasome mediated pyroptosis in mice |
| topic | microcystin-LR inflammatory bowel disease NLRP3 inflammasome pyroptosis |
| url | https://www.mdpi.com/2072-6651/15/7/447 |
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