Peroxisome proliferator-activated receptor-γ is a new therapeutic target in sepsis and inflammation

Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a member of the nuclear receptor superfamily and a ligand-activated transcription factor with pleiotropic effects on lipid metabolism, inflammation, and cell proliferation. PPAR-γ forms a heterodimer with the retinoid X receptor and upon ligand-activation binds to the PPAR response element in the promoter of genes to allow transcription. The class of insulin-sensitizing drugs known as thiazolidinediones have been identified as specific PPARγ agonists that have allowed the characterization of many genes regulated by PPARγ. Thiazolidinediones include rosiglitazone, pioglitazone, troglitazone, and ciglitazone. In addition to these synthetic agonists, cyclopentenone prostaglandins of the J(2) series have been identified as natural ligands for PPARγ. Several in vitro and in vivo studies have demonstrated that pharmacological activation of PPARγ by 15-deoxy-Δ (12,14)-PGJ(2) (15d-PGJ(2)) or thiazoliclinediones has anti-inflammatory effects. This article provides an overview of the role of PPARγ in regulating the inflammatory response and emphasizes the potential efficacy of PPAR-γ ligands as novel therapeutic approaches beyond diabetes in sepsis, inflammation, and reperfusion injury.