Papel da Angiotensina-(1-7) na inflamação aguda induzida por cristais de ácido úrico

• Ano de defesa: 2020
• Autor(a) principal: Amanda Dias Braga
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; Brasil; ICB - DEPARTAMENTO DE MORFOLOGIA; Programa de Pós-Graduação em Biologia Celular; UFMG
• Palavras-chave em Português: Artrite gotosa; Gota; Angiotensina-(1-7); Inflamação; Biologia celular; Angiotensinas
• Link de acesso: http://hdl.handle.net/1843/41332

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.