Regulation of inflammation by PPARs: a future approach to treat lung inflammatory diseases?
- 24 July 2006
- journal article
- review article
- Published by Wiley in Fundamental & Clinical Pharmacology
- Vol. 20 (5) , 429-447
- https://doi.org/10.1111/j.1472-8206.2006.00425.x
Abstract
Lung inflammatory diseases, such as acute lung injury (ALI), asthma, chronic obstructive pulmonary disease (COPD) and lung fibrosis, represent a major health problem worldwide. Although glucocorticoids are the most potent anti‐inflammatory drug in asthma, they exhibit major side effects and have poor activity in lung inflammatory disorders such as ALI or COPD. Therefore, there is growing need for the development of alternative or new therapies to treat inflammation in the lung. Peroxisome proliferator‐activated receptors (PPARs), including the three isotypes PPARα , PPARβ (or PPARδ ) and PPARγ , are transcription factors belonging to the nuclear hormone receptor superfamily. PPARs, and in particular PPARα and PPARγ , are well known for their critical role in the regulation of energy homeostasis by controlling expression of a variety of genes involved in lipid and carbohydrate metabolism. Synthetic ligands of the two receptor isotypes, the fibrates and the thiazolidinediones, are clinically used to treat dyslipidaemia and type 2 diabetes, respectively. Recently however, PPARα and PPARγ have been shown to exert a potent anti‐inflammatory activity, mainly through their ability to downregulate pro‐inflammatory gene expression and inflammatory cell functions. The present article reviews the current knowledge of the role of PPARα and PPARγ in controlling inflammation, and presents different findings suggesting that PPARα and PPARγ activators may be helpful in the treatment of lung inflammatory diseases.Keywords
This publication has 177 references indexed in Scilit:
- The role of peroxisome proliferator-activated receptor-β/δ in epithelial cell growth and differentiationCellular Signalling, 2005
- The mouse CCR2 gene is regulated by two promoters that are responsive to plasma cholesterol and peroxisome proliferator-activated receptor γ ligandsBiochemical and Biophysical Research Communications, 2005
- Oleoylethanolamide Stimulates Lipolysis by Activating the Nuclear Receptor Peroxisome Proliferator-activated Receptor α (PPAR-α)Journal of Biological Chemistry, 2004
- PPARα activation abolishes LDL-stimulated IL-8 production via AP-1 deactivation in human aortic smooth muscle cellsBiochemical and Biophysical Research Communications, 2004
- Dexamethasone induction of hypertension and diabetes is PPAR-α dependent in LDL receptor–null miceNature Medicine, 2003
- PPARγ-dependent anti-inflammatory action of rosiglitazone in human monocytes: suppression of TNFα secretion is not mediated by PTEN regulationBiochemical and Biophysical Research Communications, 2003
- PPAR agonists in the treatment of atherosclerosisCurrent Opinion in Pharmacology, 2003
- Natural ligands of PPARγ:: Are prostaglandin J2 derivatives really playing the part?Cellular Signalling, 2002
- Dual Function of Troglitazone in ICAM-1 Gene Expression in Human Vascular EndotheliumBiochemical and Biophysical Research Communications, 2001
- Activation of PPARα or γ Reduces Secretion of Matrix Metalloproteinase 9 but Not Interleukin 8 from Human Monocytic THP-1 CellsBiochemical and Biophysical Research Communications, 2000