| First Author | Chen H | Year | 2018 |
| Journal | Mol Med Rep | Volume | 17 |
| Issue | 1 | Pages | 234-242 |
| PubMed ID | 29115460 | Mgi Jnum | J:271872 |
| Mgi Id | MGI:6282249 | Doi | 10.3892/mmr.2017.7909 |
| Citation | Chen H, et al. (2018) Activation of corticotropin-releasing factor receptor 1 aggravates dextran sodium sulphate-induced colitis in mice by promoting M1 macrophage polarization. Mol Med Rep 17(1):234-242 |
| abstractText | 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 (CRFR1) 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 CRFR1 in DSStreated mice. Colonic inflammation was evaluated by determining the Disease Activity Index (DAI) and histology score. CRFR1 expression was proportional to the DAI, the histology score and the number of macrophages. Activation of CRFR1 aggravated mucosal inflammation by activating nuclear factor (NF)kappaB and subsequently increasing the expression levels of tumour necrosis factor (TNF)alpha and interleukin (IL)6. Inhibition of CRFR1 decreased the expression level of CRFR1, macrophage infiltration, NFkappaB activation, and TNFalpha and IL6 expression levels, ultimately alleviating the mucosal inflammation. Thus, CRFR1 expression was proportional to the severity of DSSinduced colitis. Activation of CRFR1 increased the DAI and histological scores of the colons from DSStreated mice by promoting M1 macrophage polarization, demonstrated as increased NFkappaB activation, and TNFalpha and IL6 release. These results provide evidence of the proinflammatory role of CRFR1 in a DSSinduced ulcerative colitis (UC) model and a possible underlying mechanism, which may facilitate the elucidation of potential treatment approaches for UC. |
