Anti-Inflammatory Action of Angiotensin 1-7 in Experimental Colitis.

Abstract

BACKGROUND:There is evidence to support a role for angiotensin (Ang) 1-7 in reducing the activity of inflammatory signaling molecules such as MAPK, PKC and SRC. Enhanced angiotensin converting enzyme 2 (ACE2) expression has been observed in patients with inflammatory bowel disease (IBD) suggesting a role in its pathogenesis, prompting this study. METHODS:The colonic expression/activity profile of ACE2, Ang 1-7, MAS1-receptor (MAS1-R), MAPK family and Akt were determined by western blot and immunofluorescence. The effect of either exogenous administration of Ang 1-7 or pharmacological inhibition of its function (by A779 treatment) was determined using the mouse dextran sulfate sodium model. RESULTS:Enhanced colonic expression of ACE2, Ang1-7 and MAS1-R was observed post-colitis induction. Daily Ang 1-7 treatment (0.01-0.06 mg/kg) resulted in significant amelioration of DSS-induced colitis. In contrast, daily administration of A779 significantly worsened features of colitis. Colitis-associated phosphorylation of p38, ERK1/2 and Akt was reduced by Ang 1-7 treatment. CONCLUSION:Our results indicate important anti-inflammatory actions of Ang 1-7 in the pathogenesis of IBD, which may provide a future therapeutic strategy to control the disease progression.