PPARs in Diseases: Control Mechanisms of Inflammation

Radina      Kostadinova; Walter      Wahli; Liliane      Michalik

doi:10.2174/092986705774462905

Abstract

The three isotypes of peroxisome proliferator-activated receptors (PPARs), PPARa, β/δ and γ, are ligand-inducible transcription factors that belong to the nuclear hormone receptor family. PPARs are implicated in the control of inflammatory responses and in energy homeostasis and thus, can be defined as metabolic and anti-inflammatory transcription factors. They exert their anti-inflammatory effects by inhibiting the induction of pro-inflammatory cytokines, adhesion molecules and extracellular matrix proteins or by stimulating the production of anti-inflammatory molecules. Furthermore, PPARs modulate the proliferation, differentiation and survival of immune cells including macrophages, B cells and T cells. This review discusses the molecular mechanisms by which PPARs and their ligands modulate the inflammatory response. In addition, it presents recent developments implicating PPAR specific ligands in potential treatments of inflammationrelated diseases, such as atherosclerosis, inflammatory bowel diseases, Parkinsons and Alzheimers diseases.

Keywords: peroxisome proliferator-activated receptors, transcription factors, molecular mechanisms, inflammatory cells, inflammatory diseases, atherosclerosis, fibrosis, cancer