| First Author | Messal N | Year | 2018 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1864 |
| Issue | 11 | Pages | 3618-3628 |
| PubMed ID | 30251681 | Mgi Jnum | J:270614 |
| Mgi Id | MGI:6277504 | Doi | 10.1016/j.bbadis.2018.08.023 |
| Citation | Messal N, et al. (2018) Ectopic expression of OX1R in ulcerative colitis mediates anti-inflammatory effect of orexin-A. Biochim Biophys Acta Mol Basis Dis 1864(11):3618-3628 |
| abstractText | Orexins (orexin-A and orexin-B) are hypothalamic peptides that are produced by the same precursor and are involved in sleep/wake control, which is mediated by two G protein-coupled receptor subtypes, OX1R and OX2R. Ulcerative colitis (UC) is an inflammatory bowel disease, (IBD) which is characterized by long-lasting inflammation and ulcers that affect the colon and rectum mucosa and is known to be a significant risk factor for colon cancer development. Based on our recent studies showing that OX1R is aberrantly expressed in colon cancer, we wondered whether orexin-A could play a role in UC. Immunohistochemistry studies revealed that OX1R is highly expressed in the affected colonic epithelium of most UC patients, but not in the non-affected colonic mucosa. Injection of exogenous orexin-A specifically improved the inflammatory symptoms in the two colitis murine models. Conversely, injection of inactive orexin-A analog, OxB7-28 or OX1R specific antagonist SB-408124 did not have anti-inflammatory effect. Moreover, treatment with orexin-A in DSS-colitis induced OX1R(-/-) knockout mice did not have any protective effect. The orexin-A anti-inflammatory effect was due to the decreased expression of pro-inflammatory cytokines in immune cells and specifically in T-cells isolated from colonic mucosa. Moreover, orexin-A inhibited canonical NFkappaB activation in an immune cell line and in intestinal epithelial cell line. These results suggest that orexin-A might represent a promising alternative to current UC therapies. |
