Peroxisome proliferator-activated receptors: potential therapeutic targets in lung disease?

Pediatr Pulmonol. 2006 Jan;41(1):23-34. doi: 10.1002/ppul.20338.

Abstract

The peroxisome proliferator-activated receptors (PPARs) are a family of nuclear hormone receptors that play central roles in lipid and glucose homeostasis, cellular differentiation, and the immune/inflammatory response. Growing evidence indicates that changes in expression and activation of PPARs likely modulate conditions as diverse as diabetes, atherosclerosis, cancer, asthma, Parkinson's disease, and Alzheimer's disease. Activation of these receptors by natural or pharmacologic ligands leads to both gene-dependent and gene-independent effects that alter the expression of a wide array of proteins. In the lung, PPARs are expressed by alveolar macrophages, as well as by epithelial, endothelial, and smooth muscle cells. Studies both in vitro and in vivo suggest that PPAR ligands may have anti-inflammatory effects in asthma, pulmonary sarcoidosis, and pulmonary alveolar proteinosis, as well as antiproliferative and antiangiogenic effects in epithelial lung cancers. Further studies to understand the contribution of these receptors to health and disease will be important for determining whether they represent a promising target for therapeutic intervention.

Publication types

  • Review

MeSH terms

  • Animals
  • Asthma / physiopathology
  • Asthma / therapy
  • Gene Expression Regulation
  • Humans
  • Inflammation Mediators / metabolism
  • Lipid Metabolism
  • Lung Diseases / physiopathology*
  • Lung Diseases / therapy*
  • Lung Neoplasms / physiopathology
  • Lung Neoplasms / therapy
  • Peroxisome Proliferator-Activated Receptors / genetics
  • Peroxisome Proliferator-Activated Receptors / immunology*
  • Peroxisome Proliferator-Activated Receptors / metabolism*
  • Polymorphism, Genetic
  • Pulmonary Alveolar Proteinosis / physiopathology
  • Pulmonary Alveolar Proteinosis / therapy
  • Sarcoidosis, Pulmonary / physiopathology
  • Sarcoidosis, Pulmonary / therapy

Substances

  • Inflammation Mediators
  • Peroxisome Proliferator-Activated Receptors