Efeito da angiotensina-(1-7) na resolução da resposta inflamatória em um modelo de artrite induzida por antígeno

Abstract

Resolution of inflammation is a crucial event that prevents tissue damage and the consequent loss of organ function. Recent studies have advanced our understanding on the role of the renin-angiotensin system in the pathogenesis of several diseases. We now recognize angiotensin-(1-7) [Ang-(1-7)] as having pivotal role in antagonizing cell proliferation, tissue fibrosis and inflammation. Using experimental models of inflammation, we provide strong data for a novel action of Ang-(1-7): resolution of inflammation in arthritis. When administered orally or directly to the site of inflammation, at the peak of the inflammatory process, Ang-(1-7) decreased neutrophil accumulation in the synovial cavity. Ang-(1-7) promoted the resolution of inflammation by inducing apoptosis of neutrophils. These effects were Mas receptor-mediated and depended on the activation of caspase and inhibition of NF-κB. Ang-(1-7) also increased the engulfment of apoptotic leukocytes, ie. efferocytosis. Altogether, our results show that Ang-(1-7) activates events that are crucial for the resolution of the inflammatory process and the return to homeostasis indicating Ang-(1-7) as a novel endogenous pro-resolving mediator.