Regulation of inflammation by PPARs: a future approach to treat lung inflammatory diseases?

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 PPAR alpha, PPAR beta (or PPAR delta) and PPAR gamma, are transcription factors belonging to the nuclear hormone receptor superfamily. PPARs, and in particular PPAR alpha and PPAR gamma, 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, PPAR alpha and PPAR gamma 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 PPAR alpha and PPAR gamma in controlling inflammation, and presents different findings suggesting that PPAR alpha and PPAR gamma activators may be helpful in the treatment of lung inflammatory diseases.