Straus Daniel S, Glass Christopher K
Biomedical Sciences Division, University of California, Riverside, Riverside, CA 92521-0121, USA.
Trends Immunol. 2007 Dec;28(12):551-8. doi: 10.1016/j.it.2007.09.003. Epub 2007 Nov 5.
The peroxisome proliferator-activated receptors (PPARalpha, -gamma, and -beta/delta) are nuclear receptors with distinct patterns of expression in many cell types both within and outside the immune system. PPAR ligands have anti-inflammatory activity in a variety of mouse models for acute and chronic inflammation. In macrophages, PPARgamma ligands repress expression of a subset of Toll-like receptor (TLR) target genes by a molecular mechanism termed ligand-dependent transrepression. In chronic inflammation, ligand-bound PPARalpha represses production of IFNgamma and IL-17 by CD4(+) T cells, and PPARgamma ligands modulate dendritic cell function to elicit the development of anergic CD4(+) T cells. PPAR ligands also repress expression of cell adhesion molecules on endothelial cells and the secretion of chemokines by epithelial and other cells, decreasing the recruitment of leukocytes to the site of inflammation. The anti-inflammatory activity of PPAR ligands in mouse models suggests their possible use for treating human inflammatory and autoimmune diseases.
过氧化物酶体增殖物激活受体（PPARα、-γ和-β/δ）是核受体，在免疫系统内外的许多细胞类型中具有不同的表达模式。PPAR配体在多种急性和慢性炎症的小鼠模型中具有抗炎活性。在巨噬细胞中，PPARγ配体通过一种称为配体依赖性反式抑制的分子机制抑制Toll样受体（TLR）靶基因子集的表达。在慢性炎症中，与配体结合的PPARα抑制CD4(+) T细胞产生IFNγ和IL-17，PPARγ配体调节树突状细胞功能以引发无反应性CD4(+) T细胞的发育。PPAR配体还抑制内皮细胞上细胞粘附分子的表达以及上皮细胞和其他细胞分泌趋化因子，减少白细胞向炎症部位的募集。PPAR配体在小鼠模型中的抗炎活性表明它们可能用于治疗人类炎症性和自身免疫性疾病。
