Peroxisome Proliferator Activator Receptor-γ Ligands, 15-Deoxy-Δ12,14-Prostaglandin J2 and Ciglitazone, Reduce Systemic Inflammation in Polymicrobial Sepsis by Modulation of Signal Transduction Pathways

摘要: Peroxisome proliferator activator receptor-γ (PPARγ) is a nuclear receptor that controls the expression of several genes involved in metabolic homeostasis. We investigated role PPARγ during inflammatory response sepsis by use ligands, 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2) and ciglitazone. Polymicrobial was induced cecal ligation puncture rats associated with hypotension, multiple organ failure, 50% mortality. markedly reduced lung thoracic aorta after sepsis. Immunohistochemistry showed positive staining for nitrotyrosine poly(ADP-ribose) synthetase aortas. Plasma levels TNF-α, IL-6, IL-10 were increased. Elevated activity myeloperoxidase found lung, colon, liver, indicating massive infiltration neutrophils. These events preceded degradation inhibitor κBα (IκBα), activation IκB kinase complex, c-Jun NH2-terminal and, subsequently, NF-κB AP-1 lung. In vivo treatment ciglitazone or 15d-PGJ2 ameliorated hypotension survival, blunted cytokine production, neutrophil liver. beneficial effects ligands reduction complex DNA binding Furthermore, up-regulated abolished formation aorta. Our data suggest attenuate through regulation pathways.