up-regulation of annexin-a1 and lipoxin a4 in individuals with ulcerative colitis may promote mucosal homeostasis老年病annexin-a1 lipoxin a4的溃疡性结肠炎患者可能促进粘膜内稳态.pdf

Up-Regulation of Annexin-A1 and Lipoxin A4 in Individuals with Ulcerative Colitis May Promote Mucosal Homeostasis 1 3 2 3 3 1 Linda Vong *, Jose G. P. Ferraz , Neil Dufton , Remo Panaccione , Paul L. Beck , Philip M. Sherman , Mauro Perretti4, John L. Wallace2 1 Hospital for Sick Children, Research Institute, Toronto, Ontario, Canada, 2 Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada, 3 Division of Gastroenterology, University of Calgary, Calgary, Alberta, Canada, 4 Centre for Biochemical Pharmacology, William Harvey Research Institute, London, United Kingdom Abstract Background: One of the characteristics of an active episode of ulcerative colitis (UC) is the intense mucosal infiltration of leukocytes. The pro-resolution mediators Annexin-A1 (AnxA1) and lipoxin A (LXA ) exert counter-regulatory effects on 4 4 leukocyte recruitment, however to date, the dual/cumulative effects of these formyl peptide receptor-2 (FPR2/ALX) agonists in the context of human intestinal diseases are unclear. To define the contribution of these mediators, we measured their expression in biopsies from individuals with UC. Methods: Colonic mucosal biopsies were collected from two broad patient groups: healthy volunteers without (‘Ctrl’ n = 20) or with a prior history of UC (‘hx of UC’ n = 5); individuals with UC experiencing active disease (‘active’ n = 8), or in medically- induced remission (‘remission’ n = 16). We assessed the mucosal expression of LXA4, AnxA1, and the FPR2/ALX