Activation of corticotropin-releasing factor receptor 1 aggravates dextran sodium sulphate-induced colitis in mice by promoting M1 macrophage polarization.

Chen, Hong; Shi, Haitao; Liu, Yaping; Ren, Xiaoyang; He, Shuixiang; Chang, Xinming; Yin, Yan

The corticotropin-releasing factor (CRF) family is involved in modulating gastrointestinal motility, sensitivity and inflammation. CRF signalling exerts an important role in inflammatory bowel disease (IBD), predominantly by activating CRF receptors. The aim of the present study was to investigate the function of CRF receptor 1 (CRF-R1) in the development of mucosal inflammation induced by dextran sulphate sodium (DSS) and the underlying mechanism. Consecutive administration of CRF or CP154526 was used to activate or block the CRF-R1 in DSS-treated mice. Colonic inflammation was evaluated by determining the Disease Activity Index (DAI) and histology score. CRF-R1 expression was proportional to the DAI, the histology score and the number of macrophages. Activation of CRF-R1 aggravated mucosal inflammation by activating nuclear factor (NF)-κB and subsequently increasing the expression levels of tumour necrosis factor (TNF)-α and interleukin (IL)-6. Inhibition of CRF-R1 decreased the expression level of CRF-R1, macrophage infiltration, NF-κB activation, and TNF-α and IL-6 expression levels, ultimately alleviating the mucosal inflammation. Thus, CRF-R1 expression was proportional to the severity of DSS-induced colitis. Activation of CRF-R1 increased the DAI and histological scores of the colons from DSS-treated mice by promoting M1 macrophage polarization, demonstrated as increased NF-κB activation, and TNF-α and IL-6 release. These results provide evidence of the pro-inflammatory role of CRF-R1 in a DSS-induced ulcerative colitis (UC) model and a possible underlying mechanism, which may facilitate the elucidation of potential treatment approaches for UC.

INFLAMMATION; CYTOKINES; ADRENOCORTICOTROPIC hormone; DEXTRAN; MACROPHAGES

Molecular Medicine Reports, 2018, Vol 17, Issue 1, p234

1791-2997

Academic Journal

10.3892/mmr.2017.7909