Avaliação dos efeitos imunomodulatórios do peptídeo sintético P140 em modelo experimental de artrite gotosa - gota

Abstract

Gout is a chronic inflammatory disease caused by the deposition of monosodium urate (MSU) crystals in joints, triggering an inflammatory response mark by increasing neutrophils in joints, inflammasome-dependent autophagy activation, and increase of hyperalgesia. The gout prevalence has grown, and this pathology does not have any effective treatment. Anti- inflammatory therapy is the most used strategy because it can stop at the beginning of acute MSU inflammatory response; however, it does not solve the problem. The P140 peptide can modulate the immune system and the autophagy response, presenting beneficial effects in lupus treatment, also a chronic inflammatory disease. Thus, the present work aims to elucidate the P140 treatment effects in a mice model of gout. Both therapeutic strategies, pre and post- treatment, decreased the neutrophil recruitment in joints, the hipernocyception, and the tissue injury in the treated mice. To better investigate the pathways and mechanisms involved, we evaluate in vitro the species reactive oxygen (ROS) production from macrophages stimulated with MSU. The P140 treatment group shows decreased ROS production than the no-treatment group, suggesting a minor inflammasome activation in these cells. In all experiments, we use a control peptide named sC140 to clarify the P140 mechanisms. Therefore, we conclude the P140 treatment show immunomodulatory effects in this mice model of gout, and this suggests this peptide be an attractive therapeutic strategy to treats this pathology.