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

Authors :
Sheng-Bing Zhao
Jia-Yi Wu
Zi-Xuan He
Yi-Hang Song
Xin Chang
Tian Xia
Xue Fang
Zhao-Shen Li
Can Xu
Shu-Ling Wang
Yu Bai
Source :
Cell Death Discovery, Vol 7, Iss 1, Pp 1-13 (2021)
Publication Year :
2021
Publisher :
Nature Publishing Group, 2021.

Abstract

Abstract 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.

Details

Language :
English
ISSN :
20587716
Volume :
7
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Cell Death Discovery
Publication Type :
Academic Journal
Accession number :
edsdoj.101336a61cf34574854816764d3f8101
Document Type :
article
Full Text :
https://doi.org/10.1038/s41420-021-00767-8