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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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Detalles Bibliográficos
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
Descripción
Sumario: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.