Ectopic expression of OX1R in ulcerative colitis mediates anti-inflammatory effect of orexin-A

Publication date: Available online 18 August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): N. Messal, N. Fernandez, S. Dayot, V. Gratio, P. Nicole, C. Prochasson, I. Chantret, G. LeGuilloux, A. Jarry, A. Couvelard, X. Tréton, T. Voisin, E. Ogier-Denis, A. CouvineauAbstractOrexins (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...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research