科研之友
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摘要
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(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. %26lt;br%26gt;Methods: Colonic mucosal biopsies were collected from two broad patient groups: healthy volunteers without (%26apos;Ctrl%26apos; n=20) or with a prior history of UC (%26apos;hx of UC%26apos; n=5); individuals with UC experiencing active disease (%26apos;active%26apos; n=8), or in medically-induced remission (%26apos;remission%26apos; 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. %26lt;br%26gt;Results: Mucosal expression of LXA(4) was elevated exclusively in biopsies from individuals in remission (3-fold, P %26lt; 0.05 vs. Ctrl). Moreover, in this same group we observed an upregulation of AnxA1 protein expression (2.5-fold increase vs. Ctrl, P %26lt;.01), concurrent with an increased level of macrophage infiltration, and an elevation in FPR2/ALX mRNA (7-fold increase vs. Ctrl, P %26lt;.05). Importantly, AnxA1 expression was not limited to cells infiltrating the lamina propria but was also detected in epithelial cells lining the intestinal crypts. %26lt;br%26gt;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 LXA(4) and AnxA1 in promoting mucosal homeostasis.
- 出版日期2012-6-18
