Dissertação
Papel da Angiotensina-(1-7) na inflamação aguda induzida por cristais de ácido úrico
Fecha
2020-02-14Autor
Amanda Dias Braga
Institución
Resumen
Gout is an inflammatory disease caused by the deposition of monosodium urate
crystals (MSU) in the joints. The acute attack of gout begins with the recognition of
MSU crystals by resident joint cells inducing a local inflammatory response triggered
by the activation of the NLRP3 inflammasome and release of IL-1β. The binding of IL-
1β to its receptor promotes the production of chemoatracting agents, resulting in the
recruitment of neutrophils that intensify the inflammatory process in the initial phases
of the response. Ang-(1-7) is a peptide from the renin-angiotensin system that is
currently highlighted for its functions in controlling the inflammatory response. Among
its actions are reducing the level of various cytokines and chemokines that leads to a
reduction or increase of cells in the joint cavity, in addition to the induction of neutrophil
apoptosis and its efferocytosis in arthritis models. The aim of this work was to evaluate
the role of Ang-(1-7) in an acute inflammation of gout. To do that, mice were submitted
to intra-articular injection of MSU crystals and treated or not with A-779, a selective
inhibitor of Ang-(1-7) receptor. The results show that Ang-(1-7) reduces the production
of inflammatory mediators and the accumulation of neutrophils in the joint in mice,
while treatment with A-779 demonstrated the role of endogenous Ang-(1-7) in
controlling the recruitment of neutrophils. Ang-(1-7) also reduced the production of IL-
1β and TNF-α in peritoneal macrophages in vitro. Results also show that Ang-(1-7)
acts directly on neutrophils, reducing cell adhesion in vivo and migration of these
leukocytes under different chemotactic stimuli, both in vivo and in vitro. Thus, Ang-(1-
7) has an anti-inflammatory role in gouty arthritis, suggesting a possible therapeutic
strategy for the treatment of acute joint inflammation induced by the deposition of MSU
crystals.