Harris S G, Phipps R P
Department of Microbiology and Immunology and James P. Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Eur J Immunol. 2001 Apr;31(4):1098-105. doi: 10.1002/1521-4141(200104)31:4<1098::aid-immu1098>3.0.co;2-i.
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.
过氧化物酶体增殖物激活受体（PPAR）-γ是一种核激素受体，作为转录因子调节脂质代谢。由于其在脂肪细胞分化中的假定作用，人们对PPAR-γ及其配体极为关注。然而，关于PPAR-γ在免疫系统尤其是T淋巴细胞中的功能却知之甚少。我们证明，来自DO11.10转基因小鼠的初始和活化的卵清蛋白特异性T细胞均表达PPAR-γ mRNA和蛋白。为了确定PPAR-γ的功能，用佛波醇12-肉豆蔻酸酯13-乙酸酯和离子霉素或抗原及抗原呈递细胞刺激T细胞。同时暴露于PPAR-γ配体（如15-脱氧-Δ（12,14）-前列腺素J2、曲格列酮）显示增殖受到强烈抑制，细胞活力显著降低。细胞活力的降低是由于T淋巴细胞凋亡，且仅在细胞用PPAR-γ而非PPAR-α激动剂处理时发生，揭示了这种反应对PPAR-γ的特异性。这些观察结果表明，PPAR-γ激动剂通过诱导凋亡在调节T细胞介导的免疫反应中起重要作用。通过PPAR-γ连接导致的T细胞死亡可能在免疫系统中作为一种有效的抗炎信号，并且配体可能用于控制发生过度炎症的疾病。
