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The nuclear receptor PPAR gamma is expressed by mouse T lymphocytes and PPAR gamma agonists induce apoptosis
1Department of Microbiology and Immunology and James P. Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Abstract:
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.
Insights
Peroxisome proliferator-activated receptor (PPAR)-gamma agonists induce T cell apoptosis, inhibiting immune responses. This suggests PPAR-gamma ligands may control inflammatory disorders by reducing T cell activity.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Peroxisome proliferator-activated receptor (PPAR)-gamma is a nuclear hormone receptor regulating lipid metabolism and adipocyte differentiation.
- The role of PPAR-gamma in the immune system, particularly in T lymphocytes, is not well understood.
Purpose of the Study:
- To investigate the function of PPAR-gamma in T lymphocytes.
- To determine the effect of PPAR-gamma ligands on T cell proliferation, viability, and apoptosis.
Main Methods:
- T cells from DO11.10-transgenic mice were analyzed for PPAR-gamma expression.
- T cells were stimulated using phorbol 12-myristate 13-acetate and ionomycin or antigen and antigen-presenting cells.
- Simultaneous treatment with PPAR-gamma ligands (15-deoxy-Delta(12,14)-prostaglandin J(2), troglitazone) or PPAR-alpha agonists was performed.
Main Results:
- Naive and activated T cells express PPAR-gamma mRNA and protein.
- PPAR-gamma ligands significantly inhibited T cell proliferation and decreased cell viability.
- The decrease in cell viability was attributed to apoptosis, specifically induced by PPAR-gamma agonists, not PPAR-alpha agonists.
Conclusions:
- PPAR-gamma agonists induce T lymphocyte apoptosis, playing a key role in regulating T cell-mediated immune responses.
- T cell apoptosis mediated by PPAR-gamma ligation may function as an anti-inflammatory signal.
- PPAR-gamma ligands could potentially be utilized to manage inflammatory disorders.