sq-23377 and pirinixic-acid

Peroxisome proliferator-activated receptor (PPAR)-gamma is a nuclear hormone receptor that serves as a trans factor to regulate lipid metabolism. Intense interest is focused on PPAR-gamma and its ligands owing to its putative role in adipocyte differentiation. Little is known, however, about the functions of PPAR-gamma in the immune system, especially in T lymphocytes. We demonstrate that both naive and activated ovalbumin-specific T cells from DO11.10-transgenic mice express PPAR-gamma mRNA and protein. In order to determine the function of PPAR-gamma, T cells were stimulated with phorbol 12-myristate 13-acetate and ionomycin or antigen and antigen-presenting cells. Simultaneous exposure to PPAR-gamma ligands (e. g. 15-deoxy-Delta(12, 14)-prostaglandin J(2), troglitazone) showed drastic inhibition of proliferation and significant decreases in cell viability. The decrease in cell viability was due to apoptosis of the T lymphocytes, and occurred only when cells were treated with PPAR-gamma, and not PPAR-alpha agonists, revealing specificity of this response for PPAR-gamma. These observations suggest that PPAR-gamma agonists play an important role in regulating T cell-mediated immune responses by inducing apoptosis. T cell death via PPAR-gamma ligation may act as a potent anti-inflammatory signal in the immune system, and ligands could possibly be used to control disorders in which excessive inflammation occurs.

Topics: Animals; Antigen Presentation; Apoptosis; Cell Division; Cell Survival; Cells, Cultured; Chromans; Flow Cytometry; Immunohistochemistry; In Situ Nick-End Labeling; Ionomycin; Ligands; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Transgenic; Prostaglandin D2; Pyrimidines; Receptors, Cytoplasmic and Nuclear; RNA, Messenger; Specific Pathogen-Free Organisms; T-Lymphocytes; Tetradecanoylphorbol Acetate; Thiazoles; Thiazolidinediones; Transcription Factors; Troglitazone