Rol modulador del Receptor Activado por Factores de Proliferación Peroxisomal de tipo gamma (PPARγ) en la respuesta inflamatoria cardiaca

[摘要] Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent nuclear transcription factors that have been implicated in the regulation of lipid and glucose metabolism, differentiation, homeostasis and control of the inflammatory response. 15-deoxy-∆12,14 Prostaglandin J2 (15dPGJ2), natural PPARγ ligand, has high affinity for PPARγ and has been proposed as a regulator of the inflammatory response. In this work we studied the role of 15dPGJ2 in the resolution of inflammation of neonatal cardiac cells in two experimental models: one of endotoxic shock generated by lipopolysaccharide (LPS) from Escherichia coli and the other of Trypanosoma cruzi (T. cruzi) acute infection. Our results show that 15dPGJ2 modulates inflammation by inhibiting inflammatory enzymes such as Nitric Oxide (NO) Synthase 2 (NOS-2), Cyclooxygenase 2 (COX-2) and Metalloproteases (MMP-9 and MMP-2) induced by LPS or by T. cruzi infection. Moreover, pre treatment of cardiomyocytes with PPARγ agonist inhibits the synthesis of proinflammatory cytokines like Interleukin-6 (IL-6) and Tumor Necrosis Factor-α (TNF-α), MMP-9 and MMP-2 activities and NO production. Moreover, we observed that pre treatment of cardiomyocytes with GW9662, a PPARγ specific antagonist, prevented 15dPGJ2 inhibitory effects on the inflammatory response. PPARγ role in inflammation was confirmed through transfection of cardiomyocytes with PPARγ-small interfering RNA (PPARγ-siRNA). Our results show that transfection impairs the effects of 15dPGJ2 in the regulation of inflammatory response. Our data point out 15dPGJ2 as a potent modulator of cardiac inflammation in both experimental models.

[学科分类] 生物技术

[关键词] PPARγ;15dPGJ2;cardiomyocytes;inflammation;NOS-2;COX-2;MMPs