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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...

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Autores principales: Zhang, Tao, Jiang, Junhang, Liu, Jingting, Xu, Lu, Duan, Shixin, Sun, Lei, Zhao, Wenjuan, Qian, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
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.
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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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