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MK2 Is Required for Neutrophil-Derived ROS Production and Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) is a chronic disease that is commonly accompanied by increased inflammatory responses and elevated reactive oxygen species (ROS) of the gastrointestinal tract. Here, we found that MAPK-activated protein kinase 2 (MK2) modulates ROS production and is required for dext...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303912/ https://www.ncbi.nlm.nih.gov/pubmed/32596245 http://dx.doi.org/10.3389/fmed.2020.00207 |
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author | Zhang, Tao Jiang, Junhang Liu, Jingting Xu, Lu Duan, Shixin Sun, Lei Zhao, Wenjuan Qian, Feng |
author_facet | Zhang, Tao Jiang, Junhang Liu, Jingting Xu, Lu Duan, Shixin Sun, Lei Zhao, Wenjuan Qian, Feng |
author_sort | Zhang, Tao |
collection | PubMed |
description | Inflammatory bowel disease (IBD) is a chronic disease that is commonly accompanied by increased inflammatory responses and elevated reactive oxygen species (ROS) of the gastrointestinal tract. Here, we found that MAPK-activated protein kinase 2 (MK2) modulates ROS production and is required for dextran sulfate sodium (DSS)-induced IBD in the mouse model. Genetic ablation of MK2 in the myeloid lineage cells (MK2(Lyz2−KO)) protected against DSS-induced colitis injury. In response to DSS challenge, compared to MK2(lyz2−WT) mice, MK2(Lyz2−KO) mice exhibited less damage of epithelial and goblet cells, decreased generation of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and ROS, as well as reduced Ki67-positive cells and concentrations of myeloperoxidase (MPO) in the intestinal epithelium. Furthermore, upon treatment with formylated peptide N-formyl-methionyl-leucyl-phenylalanine (fMLF), the generation of ROS was attenuated in MK2-deficient neutrophils, in which the phosphorylation of Akt and p38 MAPK was also reduced. Collectively, these findings indicated that MK2 is required for neutrophil-derived ROS production and IBD, and MK2 and ROS are promising therapeutic targets for IBD. |
format | Online Article Text |
id | pubmed-7303912 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-73039122020-06-26 MK2 Is Required for Neutrophil-Derived ROS Production and Inflammatory Bowel Disease Zhang, Tao Jiang, Junhang Liu, Jingting Xu, Lu Duan, Shixin Sun, Lei Zhao, Wenjuan Qian, Feng Front Med (Lausanne) Medicine Inflammatory bowel disease (IBD) is a chronic disease that is commonly accompanied by increased inflammatory responses and elevated reactive oxygen species (ROS) of the gastrointestinal tract. Here, we found that MAPK-activated protein kinase 2 (MK2) modulates ROS production and is required for dextran sulfate sodium (DSS)-induced IBD in the mouse model. Genetic ablation of MK2 in the myeloid lineage cells (MK2(Lyz2−KO)) protected against DSS-induced colitis injury. In response to DSS challenge, compared to MK2(lyz2−WT) mice, MK2(Lyz2−KO) mice exhibited less damage of epithelial and goblet cells, decreased generation of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and ROS, as well as reduced Ki67-positive cells and concentrations of myeloperoxidase (MPO) in the intestinal epithelium. Furthermore, upon treatment with formylated peptide N-formyl-methionyl-leucyl-phenylalanine (fMLF), the generation of ROS was attenuated in MK2-deficient neutrophils, in which the phosphorylation of Akt and p38 MAPK was also reduced. Collectively, these findings indicated that MK2 is required for neutrophil-derived ROS production and IBD, and MK2 and ROS are promising therapeutic targets for IBD. Frontiers Media S.A. 2020-06-12 /pmc/articles/PMC7303912/ /pubmed/32596245 http://dx.doi.org/10.3389/fmed.2020.00207 Text en Copyright © 2020 Zhang, Jiang, Liu, Xu, Duan, Sun, Zhao and Qian. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Medicine Zhang, Tao Jiang, Junhang Liu, Jingting Xu, Lu Duan, Shixin Sun, Lei Zhao, Wenjuan Qian, Feng MK2 Is Required for Neutrophil-Derived ROS Production and Inflammatory Bowel Disease |
title | MK2 Is Required for Neutrophil-Derived ROS Production and Inflammatory Bowel Disease |
title_full | MK2 Is Required for Neutrophil-Derived ROS Production and Inflammatory Bowel Disease |
title_fullStr | MK2 Is Required for Neutrophil-Derived ROS Production and Inflammatory Bowel Disease |
title_full_unstemmed | MK2 Is Required for Neutrophil-Derived ROS Production and Inflammatory Bowel Disease |
title_short | MK2 Is Required for Neutrophil-Derived ROS Production and Inflammatory Bowel Disease |
title_sort | mk2 is required for neutrophil-derived ros production and inflammatory bowel disease |
topic | Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303912/ https://www.ncbi.nlm.nih.gov/pubmed/32596245 http://dx.doi.org/10.3389/fmed.2020.00207 |
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