Peroxisome proliferator-activated receptor gamma agonists as therapy for chronic airway inflammation.
Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily. PPARgamma 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 PPARgamma 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, PPARgamma 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 PPARgamma 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 PPARgamma ligands and discuss their potential therapeutic effects in animal models of inflammatory airway disease.
Belvisi
Maria G
MG
Respiratory Pharmacology, Airway Diseases, National Heart and Lung Institute, Faculty of Medicine, Imperial College, Guy Scadding Building, Dovehouse Street, London, SW3 6LY UK. m.belvisi@imperial.ac.uk
Hele
David J
DJ
Birrell
Mark A
MA
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D008024:Ligands; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000188:drug therapy* / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use
C477819:15-deoxyprostaglandin J2; C496142:3-(2,4-dichlorobenzyl)-2-methyl-N-(pentylsulfonyl)-3 H-benzimidazole-5-carboxamide; D000893:Anti-Inflammatory Agents; D001562:Benzimidazoles; D005227:Fatty Acids; D008024:Ligands; D047495:PPAR gamma; D045162:Thiazolidinediones; D015230:Prostaglandin D2