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METTL3 Regulates the Inflammatory Response in CPB2 Toxin-Exposed IPEC-J2 Cells through the TLR2/NF-κB Signaling Pathway

Clostridium perfringens beta2 (CPB2) toxin is one of the main pathogenic toxins produced by Clostridium perfringens, which causes intestinal diseases in animals and humans. The N6-methyladenosine (m6A) modification is the most common reversible modification in eukaryotic disease processes. Methyltra...

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Autores principales: Zhang, Juanli, Yang, Jiaojiao, Gao, Xiaoli, Huang, Xiaoyu, Luo, Ruirui, Yang, Qiaoli, Yan, Zunqiang, Wang, Pengfei, Wang, Wei, Xie, Kaihui, Li, Jie, Zhang, Bo, Gun, Shuangbao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9781724/
https://www.ncbi.nlm.nih.gov/pubmed/36555481
http://dx.doi.org/10.3390/ijms232415833
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author Zhang, Juanli
Yang, Jiaojiao
Gao, Xiaoli
Huang, Xiaoyu
Luo, Ruirui
Yang, Qiaoli
Yan, Zunqiang
Wang, Pengfei
Wang, Wei
Xie, Kaihui
Li, Jie
Zhang, Bo
Gun, Shuangbao
author_facet Zhang, Juanli
Yang, Jiaojiao
Gao, Xiaoli
Huang, Xiaoyu
Luo, Ruirui
Yang, Qiaoli
Yan, Zunqiang
Wang, Pengfei
Wang, Wei
Xie, Kaihui
Li, Jie
Zhang, Bo
Gun, Shuangbao
author_sort Zhang, Juanli
collection PubMed
description Clostridium perfringens beta2 (CPB2) toxin is one of the main pathogenic toxins produced by Clostridium perfringens, which causes intestinal diseases in animals and humans. The N6-methyladenosine (m6A) modification is the most common reversible modification in eukaryotic disease processes. Methyltransferase-like 3 (METTL3) regulates immunity and inflammatory responses induced by the bacterial infections in animals. However, METTL3′s involvement in CPB2-treated intestinal porcine epithelial cell line-J2 (IPEC-J2) remains unclear. In the current study, we used methylated RNA immunoprecipitation-quantitative polymerase chain reaction, Western blotting and immunofluorescence assay to determine the role of METTL3 in CPB2-exposed IPEC-J2 cells. The findings revealed that m6A and METTL3 levels were increased in CPB2 treated IPEC-J2 cells. Functionally, METTL3 overexpression promoted the release of inflammatory factors, increased cytotoxicity, decreased cell viability and disrupted tight junctions between cells, while the knockdown of METTL3 reversed these results. Furthermore, METTL3 was involved in the inflammatory response of IPEC-J2 cells by activating the TLR2/NF-κB signaling pathway through regulating TLR2 m6A levels. In conclusion, METTL3 overexpression triggered the TLR2/NF-κB signaling pathway and promoted CPB2-induced inflammatory responses in IPEC-J2 cells. These findings may provide a new strategy for the prevention and treatment of diarrhea caused by Clostridium perfringens.
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spelling pubmed-97817242022-12-24 METTL3 Regulates the Inflammatory Response in CPB2 Toxin-Exposed IPEC-J2 Cells through the TLR2/NF-κB Signaling Pathway Zhang, Juanli Yang, Jiaojiao Gao, Xiaoli Huang, Xiaoyu Luo, Ruirui Yang, Qiaoli Yan, Zunqiang Wang, Pengfei Wang, Wei Xie, Kaihui Li, Jie Zhang, Bo Gun, Shuangbao Int J Mol Sci Article Clostridium perfringens beta2 (CPB2) toxin is one of the main pathogenic toxins produced by Clostridium perfringens, which causes intestinal diseases in animals and humans. The N6-methyladenosine (m6A) modification is the most common reversible modification in eukaryotic disease processes. Methyltransferase-like 3 (METTL3) regulates immunity and inflammatory responses induced by the bacterial infections in animals. However, METTL3′s involvement in CPB2-treated intestinal porcine epithelial cell line-J2 (IPEC-J2) remains unclear. In the current study, we used methylated RNA immunoprecipitation-quantitative polymerase chain reaction, Western blotting and immunofluorescence assay to determine the role of METTL3 in CPB2-exposed IPEC-J2 cells. The findings revealed that m6A and METTL3 levels were increased in CPB2 treated IPEC-J2 cells. Functionally, METTL3 overexpression promoted the release of inflammatory factors, increased cytotoxicity, decreased cell viability and disrupted tight junctions between cells, while the knockdown of METTL3 reversed these results. Furthermore, METTL3 was involved in the inflammatory response of IPEC-J2 cells by activating the TLR2/NF-κB signaling pathway through regulating TLR2 m6A levels. In conclusion, METTL3 overexpression triggered the TLR2/NF-κB signaling pathway and promoted CPB2-induced inflammatory responses in IPEC-J2 cells. These findings may provide a new strategy for the prevention and treatment of diarrhea caused by Clostridium perfringens. MDPI 2022-12-13 /pmc/articles/PMC9781724/ /pubmed/36555481 http://dx.doi.org/10.3390/ijms232415833 Text en © 2022 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
Zhang, Juanli
Yang, Jiaojiao
Gao, Xiaoli
Huang, Xiaoyu
Luo, Ruirui
Yang, Qiaoli
Yan, Zunqiang
Wang, Pengfei
Wang, Wei
Xie, Kaihui
Li, Jie
Zhang, Bo
Gun, Shuangbao
METTL3 Regulates the Inflammatory Response in CPB2 Toxin-Exposed IPEC-J2 Cells through the TLR2/NF-κB Signaling Pathway
title METTL3 Regulates the Inflammatory Response in CPB2 Toxin-Exposed IPEC-J2 Cells through the TLR2/NF-κB Signaling Pathway
title_full METTL3 Regulates the Inflammatory Response in CPB2 Toxin-Exposed IPEC-J2 Cells through the TLR2/NF-κB Signaling Pathway
title_fullStr METTL3 Regulates the Inflammatory Response in CPB2 Toxin-Exposed IPEC-J2 Cells through the TLR2/NF-κB Signaling Pathway
title_full_unstemmed METTL3 Regulates the Inflammatory Response in CPB2 Toxin-Exposed IPEC-J2 Cells through the TLR2/NF-κB Signaling Pathway
title_short METTL3 Regulates the Inflammatory Response in CPB2 Toxin-Exposed IPEC-J2 Cells through the TLR2/NF-κB Signaling Pathway
title_sort mettl3 regulates the inflammatory response in cpb2 toxin-exposed ipec-j2 cells through the tlr2/nf-κb signaling pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9781724/
https://www.ncbi.nlm.nih.gov/pubmed/36555481
http://dx.doi.org/10.3390/ijms232415833
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