[HTML][HTML] Up-Regulation of Annexin-A1 and Lipoxin A4 in Individuals with Ulcerative Colitis May Promote Mucosal Homeostasis
L Vong, JGP Ferraz, N Dufton, R Panaccione… - PLoS …, 2012 - journals.plos.org
PLoS One, 2012•journals.plos.org
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 A4 (LXA4) 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. Methods …
intense mucosal infiltration of leukocytes. The pro-resolution mediators Annexin-A1 (AnxA1)
and lipoxin A4 (LXA4) 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. Methods …
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 A4 (LXA4) 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.
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 receptor in each patient group using a combination of fluorescence microscopy, biochemical and molecular analyses.
Results
Mucosal expression of LXA4 was elevated exclusively in biopsies from individuals in remission (3-fold, P<0.05 vs. Ctrl). Moreover, in this same group we observed an upregulation of AnxA1 protein expression (2.5-fold increase vs. Ctrl, P<.01), concurrent with an increased level of macrophage infiltration, and an elevation in FPR2/ALX mRNA (7-fold increase vs. Ctrl, P<.05). Importantly, AnxA1 expression was not limited to cells infiltrating the lamina propria but was also detected in epithelial cells lining the intestinal crypts.
Conclusions
Our results demonstrate a specific up-regulation of this pro-resolution circuit in individuals in remission from UC, and suggest a significant role for LXA4 and AnxA1 in promoting mucosal homeostasis.
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