Belvisi Maria G, Hele David J, Birrell Mark A
Respiratory Pharmacology, Airway Diseases, National Heart and Lung Institute, Faculty of Medicine, Imperial College, Guy Scadding Building, Dovehouse Street, London, SW3 6LY UK.
Eur J Pharmacol. 2006 Mar 8;533(1-3):101-9. doi: 10.1016/j.ejphar.2005.12.048. Epub 2006 Feb 3.
Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily. PPARgamma regulates several metabolic pathways by binding to sequence-specific PPAR response elements in the promoter region of target genes, including lipid biosynthesis and glucose metabolism. Synthetic PPARgamma agonists have been developed, such as the thiazolidinediones rosiglitazone and pioglitazone. These act as insulin sensitizers and are used in the treatment of type 2 diabetes. Recently however, PPARgamma ligands have been implicated as regulators of cellular inflammatory and immune responses. They are thought to exert anti-inflammatory effects by negatively regulating the expression of pro-inflammatory genes. Several studies have demonstrated that PPARgamma ligands possess anti-inflammatory properties and that these properties may prove helpful in the treatment of inflammatory diseases of the airways. This review will outline the anti-inflammatory effects of synthetic and endogenous PPARgamma ligands and discuss their potential therapeutic effects in animal models of inflammatory airway disease.
过氧化物酶体增殖物激活受体γ（PPARγ）是一种配体激活的转录因子，属于核激素受体超家族。PPARγ通过与靶基因启动子区域的序列特异性PPAR反应元件结合来调节多种代谢途径，包括脂质生物合成和葡萄糖代谢。已经开发出合成的PPARγ激动剂，如噻唑烷二酮类的罗格列酮和吡格列酮。这些药物作为胰岛素增敏剂，用于治疗2型糖尿病。然而，最近PPARγ配体被认为是细胞炎症和免疫反应的调节剂。它们被认为通过负向调节促炎基因的表达发挥抗炎作用。多项研究表明，PPARγ配体具有抗炎特性，这些特性可能有助于治疗气道炎症性疾病。本综述将概述合成和内源性PPARγ配体的抗炎作用，并讨论它们在炎症性气道疾病动物模型中的潜在治疗作用。
