Division of Rheumatic Diseases, Department of Medicine, University of Connecticut Health Center, Farmington
Correspondence: Robert B. Clark, M.D., Division of Rheumatic Diseases, Department of Medicine, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030. E-mail: rclark{at}nso2.uchc.edu
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. PPAR
and PPAR
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 PPAR in the responses of T
lymphocytes. Ligands for PPAR 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
PPAR, inflammation, and immunity is that ligands thought to be
specific for PPAR may have regulatory effects on inflammatory
parameters that are PPAR-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.
Key Words: T cells • macrophages • endothelial cells • thiazolidinediones
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