Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Yang, Yue, Gong, Pan, Long, Xiuyan, Jiang, Yuanjuan, Ye, Mingmei, Tao, Sifan, Su, Yahui, Yang, Fei, Tian, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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
_version_ 1785099037762912256
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
work_keys_str_mv AT yangyue microcystinlrinducesandaggravatescolitisthroughnlrp3inflammasomemediatedpyroptosisinmice
AT gongpan microcystinlrinducesandaggravatescolitisthroughnlrp3inflammasomemediatedpyroptosisinmice
AT longxiuyan microcystinlrinducesandaggravatescolitisthroughnlrp3inflammasomemediatedpyroptosisinmice
AT jiangyuanjuan microcystinlrinducesandaggravatescolitisthroughnlrp3inflammasomemediatedpyroptosisinmice
AT yemingmei microcystinlrinducesandaggravatescolitisthroughnlrp3inflammasomemediatedpyroptosisinmice
AT taosifan microcystinlrinducesandaggravatescolitisthroughnlrp3inflammasomemediatedpyroptosisinmice
AT suyahui microcystinlrinducesandaggravatescolitisthroughnlrp3inflammasomemediatedpyroptosisinmice
AT yangfei microcystinlrinducesandaggravatescolitisthroughnlrp3inflammasomemediatedpyroptosisinmice
AT tianli microcystinlrinducesandaggravatescolitisthroughnlrp3inflammasomemediatedpyroptosisinmice