Kostadinova Radina, Wahli Walter, Michalik Liliane
Center for Integrative Genomics, NCCR Frontiers in Genetics, University of Lausanne, CH-1015 Lausanne, Switzerland.
Curr Med Chem. 2005;12(25):2995-3009. doi: 10.2174/092986705774462905.
The three isotypes of peroxisome proliferator-activated receptors (PPARs), PPARalpha, beta/delta and gamma, 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 inflammation-related diseases, such as atherosclerosis, inflammatory bowel diseases, Parkinson's and Alzheimer's diseases.
过氧化物酶体增殖物激活受体(PPARs)的三种同型异构体,即PPARα、β/δ和γ,是属于核激素受体家族的配体诱导型转录因子。PPARs参与炎症反应的调控以及能量稳态的维持,因此可被定义为代谢和抗炎转录因子。它们通过抑制促炎细胞因子、黏附分子和细胞外基质蛋白的诱导,或通过刺激抗炎分子的产生来发挥抗炎作用。此外,PPARs调节包括巨噬细胞、B细胞和T细胞在内的免疫细胞的增殖、分化和存活。本综述讨论了PPARs及其配体调节炎症反应的分子机制。此外,还介绍了PPAR特异性配体在动脉粥样硬化、炎症性肠病、帕金森病和阿尔茨海默病等炎症相关疾病潜在治疗中的最新进展。