Up-regulation of Annexin-A1 and lipoxin A(4) in individuals with ulcerative colitis may promote mucosal homeostasis.

Abstract

BackgroundOne 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(4) (LXA(4)) exert counter-regulatory effects on 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.MethodsColonic 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 LXA(4), AnxA1, and the FPR2/ALX receptor in each patient group using a combination of fluorescence microscopy, biochemical and molecular analyses.ResultsMucosal expression of LXA(4) was elevated exclusively in biopsies from individuals in remission (3-fold, PConclusionsOur results demonstrate a specific up-regulation of this pro-resolution circuit in individuals in remission from UC, and suggest a significant role for LXA(4) and AnxA1 in promoting mucosal homeostasis.