Corticotropin releasing hormone promotes inflammatory bowel disease via inducing intestinal macrophage autophagy

Psychosocial stress is a vital factor contributing to the pathogenesis and progression of inflammatory bowel disease (IBD). The contribution of intestinal macrophage autophagy to the onset and development of IBD has been widely studied. Herein, we investigated the underlying mechanism of psychosocia...

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Bibliographic Details
Published in:Cell death discovery 2021-12, Vol.7 (1), p.377-377, Article 377
Main Authors: Zhao, Sheng-Bing, Wu, Jia-Yi, He, Zi-Xuan, Song, Yi-Hang, Chang, Xin, Xia, Tian, Fang, Xue, Li, Zhao-Shen, Xu, Can, Wang, Shu-Ling, Bai, Yu
Format: Article
Language:English
Subjects:
692/420/256/2516
692/699/1503/257/1389
Apoptosis
Autophagy
Biochemistry
Biomedical and Life Sciences
Bone marrow
Cell Biology
Cell Cycle Analysis
Chloroquine
Corticotropin-releasing hormone
Dextran
Dextran sulfate
Inflammatory bowel disease
Inflammatory bowel diseases
Intestine
Life Sciences
Lipopolysaccharides
Macrophages
Phagocytosis
Social interactions
Stem Cells
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Summary:Psychosocial stress is a vital factor contributing to the pathogenesis and progression of inflammatory bowel disease (IBD). The contribution of intestinal macrophage autophagy to the onset and development of IBD has been widely studied. Herein, we investigated the underlying mechanism of psychosocial stress in an IBD mouse model pertaining to macrophage autophagy. Corticotropin releasing hormone (CRH) was peripherally administrated to induce psychosocial stress. For in vivo studies, dextran sulfate sodium (DSS) was used for the creation of our IBD mouse model. For in vitro studies, lipopolysaccharide (LPS) was applied on murine bone marrow-derived macrophages (BMDMs) as a cellular IBD-related challenge. Chloroquine was applied to inhibit autophagy. We found that CRH aggravated the severity of DSS-induced IBD, increasing overall and local inflammatory reactions and infiltration. The levels of autophagy in intestinal macrophages and murine BMDMs were increased under these IBD-related inflammatory challenges and CRH further enhanced these effects. Subsequent administration of chloroquine markedly attenuated the detrimental effects of CRH on IBD severity and inflammatory reactions via inhibition of autophagy. These findings illustrate the effects of peripheral administration of CRH on DSS-induced IBD via the enhancement of intestinal macrophage autophagy, thus providing a novel understanding as well as therapeutic target for the treatment of IBD.
ISSN:2058-7716
2058-7716
DOI:10.1038/s41420-021-00767-8