Anti-inflammatory action of angiotensin 1-7 in experimental colitis may be mediated through modulation of serum cytokines/chemokines and immune cell functions

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Abstract

We recently demonstrated Ang 1–7 reduced inflammation in the dextran sulfate sodium (DSS) colitis model. In this study we examined the effect of Ang 1–7 on modulation of plasma levels of selected cytokines and chemokines and immune cell effector functions (apoptosis, chemotaxis and superoxide release) in vitro. The degree of neutrophil recruitment to the colon was assessed by immunofluorescence and myeloperoxidase activity. Daily Ang 1–7 treatment at 0.01 mg/kg dose which previously ameliorated colitis severity, showed a significant reduction in circulating levels of several cytokines and chemokines, and neutrophil recruitment to the colonic tissue. It also significantly enhanced immune cell apoptosis, and reduced neutrophil chemotaxis and superoxide release in vitro. In contrast, daily administration of the Ang 1–7R antagonist A779 which previously worsened colitis severity showed significant up-regulation of specific mediators. Our results demonstrate a novel anti-inflammatory action of Ang 1–7 through modulation of plasma levels of cytokines/chemokines and immune cell activity.

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