PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS

Abstract

Peroxisome proliferator-activated receptors (PPARs) are members of the ligand-activated nuclear hormone receptor superfamily of transcription factors that includes receptors for steroids, thyroid hormone, retinoic acid, and vitamin D. Upon activation in the cytoplasm, PPARs heterodimerize with retinoid X receptors (RXR) and form a complex that translocates to the nucleus and regulates gene expression. PPARs are thought to play roles in diverse physiological processes ranging from lipid metabolism to inflammation, and have been implicated in diseases such as cancer, atherosclerosis, and diabetes. Although information about the function of PPARs in lung is scarce, data implicating these molecules in key processes in lung biology are rapidly emerging. In lung, PPARs are expressed by recruited immune cells (e.g., monocytes) and in resident cells such as tissue macrophages, bronchial and alveolar epithelial cells, endothelium, and airway smooth muscle, among other cell types. Of the three PPAR forms (PPAR- α , PPAR- β / δ , PPAR- γ ), PPAR- γ is the best studied, and it is believed to regulate cellular differentiation and proliferation. Several studies suggest that PPAR- γ serves to downregulate lung inflammation, promotes vascular function, and acts as a tumor suppressor in lung and other carcinomas.