Peroxisome proliferator-activated receptor gamma agonists as therapy for chronic airway inflammation

Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily. PPAR gamma regulates several metabolic pathways by binding to sequence-specific PPAR response elements in the promoter region of target genes, including lipid biosynthesis and glucose metabolism. Synthetic PPAR gamma agonists have been developed, such as the thiazolidinediones rosiglitazone and pioglitazone. These act as insulin sensitizers and are used in the treatment of type 2 diabetes. Recently however, PPAR gamma ligands have been implicated as regulators Of cellular inflammatory and immune responses. They are thought to exert anti-inflammatory effects by negatively regulating the expression of pro-inflammatory genes. Several Studies have demonstrated that PPAR gamma ligands possess anti-inflammatory properties and that these properties may prove helpful in the treatment of inflammatory diseases of the airways. This review will outline the anti-inflammatory effects of synthetic and endogenous PPAR gamma ligands and discuss their potential therapeutic effects in animal models of inflammatory airway disease. (c) 2006 Elsevier B.V. All rights reserved.