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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10467093/ https://www.ncbi.nlm.nih.gov/pubmed/37505716 http://dx.doi.org/10.3390/toxins15070447 |
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author | Yang, Yue Gong, Pan Long, Xiuyan Jiang, Yuanjuan Ye, Mingmei Tao, Sifan Su, Yahui Yang, Fei Tian, Li |
author_facet | Yang, Yue Gong, Pan Long, Xiuyan Jiang, Yuanjuan Ye, Mingmei Tao, Sifan Su, Yahui Yang, Fei Tian, Li |
author_sort | Yang, Yue |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-10467093 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-104670932023-08-31 Microcystin-LR Induces and Aggravates Colitis through NLRP3 Inflammasome-Mediated Pyroptosis in Mice Yang, Yue Gong, Pan Long, Xiuyan Jiang, Yuanjuan Ye, Mingmei Tao, Sifan Su, Yahui Yang, Fei Tian, Li Toxins (Basel) Article 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. MDPI 2023-07-06 /pmc/articles/PMC10467093/ /pubmed/37505716 http://dx.doi.org/10.3390/toxins15070447 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yang, Yue Gong, Pan Long, Xiuyan Jiang, Yuanjuan Ye, Mingmei Tao, Sifan Su, Yahui Yang, Fei Tian, Li Microcystin-LR Induces and Aggravates Colitis through NLRP3 Inflammasome-Mediated Pyroptosis in Mice |
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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10467093/ https://www.ncbi.nlm.nih.gov/pubmed/37505716 http://dx.doi.org/10.3390/toxins15070447 |
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