The role of PPARs in inflammation and immunity

The family of transcription factors termed peroxisome proliferator-activated receptors (PPARs) has recently been the focus of much interest for their possible role in the regulation of inflammation and immune responses. PPARalpha and PPARgamma have been implicated in the regulation of macrophage and endothelial cell inflammatory responses. Although PPAR activation has generally been shown to have anti-inflammatory effects, opposite effects have been noted, and results often appear to depend on the ligands being used and the inflammatory parameters being measured. Recently, my laboratory and others have described a role for PPARgamma in the responses of T lymphocytes. Ligands for PPARgamma have been found to inhibit proliferation of activated T cells, and this appears to involve inhibition of IL-2 secretion and/or the induction of apoptosis. However, one problem in the interpretation of many of the studies of PPARgamma, inflammation, and immunity is that ligands thought to be specific for PPARgamma may have regulatory effects on inflammatory parameters that are PPARgamma-independent. Future studies of the role of the PPARs in inflammatory and immune responses should include further studies of T cells, T-cell subsets, and dendritic cells but will have to re-examine the issue of PPAR specificity of the ligands being used. This may require further knockout studies and technology, together with the identification of endogenous and perhaps more specific synthetic PPAR ligands.