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

Eur J Pharmacol. 2006 Mar 8;533(1-3):101-9. doi: 10.1016/j.ejphar.2005.12.048. Epub 2006 Feb 3.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Asthma / drug therapy*
  • Asthma / metabolism
  • Benzimidazoles / pharmacology
  • Benzimidazoles / therapeutic use
  • Clinical Trials as Topic
  • Disease Models, Animal
  • Fatty Acids / metabolism
  • Humans
  • Ligands
  • PPAR gamma / agonists*
  • PPAR gamma / metabolism
  • Prostaglandin D2 / analogs & derivatives
  • Prostaglandin D2 / metabolism
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / metabolism
  • Pulmonary Fibrosis / drug therapy*
  • Pulmonary Fibrosis / metabolism
  • Thiazolidinediones / pharmacology
  • Thiazolidinediones / therapeutic use

Substances

  • 15-deoxyprostaglandin J2
  • 3-(2,4-dichlorobenzyl)-2-methyl-N-(pentylsulfonyl)-3 H-benzimidazole-5-carboxamide
  • Anti-Inflammatory Agents
  • Benzimidazoles
  • Fatty Acids
  • Ligands
  • PPAR gamma
  • Thiazolidinediones
  • Prostaglandin D2