Anti-inflammatory actions of PPAR ligands: new insights on cellular and molecular mechanisms.

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.