Regulation of interleukin 2 synthesis by cAMP in human T cells.
Regulation of interleukin 2 synthesis by cAMP in human T cells.
复制标题
cAMP 在人类 T 细胞中调节白细胞介素 2 的合成。
作者：
D. Mary;C. Aussel;B. Ferruà;M. Fehlmann
T 细胞激活需要两个初始信号，首先导致白细胞介素 2 (IL 2) 受体的表达和 IL 2 合成的启动，然后导致 T 细胞增殖。 Jurkat T 淋巴瘤细胞已被证明是研究 IL 2 合成的良好模型，因为这些细胞也需要两个信号来激活。第一个信号可以由凝集素植物血凝素 (PHA) 提供，第二个信号可以由佛波酯 12-o-十四烷酰佛波醇 13-乙酸酯 (TPA) 提供。然而，Jurkat 细胞中 IL 2 合成的调节尚不清楚，本研究涉及 cAMP 对 IL 2 合成的作用。在 Jurkat 细胞中，IL 2 合成似乎受到腺苷酸环化酶活性的高度调节。这通过使用不同的方法来增加细胞内cAMP水平得到证明，即通过使用渗透性cAMP类似物、使用腺苷酸环化酶激活剂毛喉素、使用刺激性GTP结合蛋白霍乱毒素的α亚基激活剂以及使用磷酸二酯酶抑制剂。此外，前列腺素 E1 和 E2 可以特异性结合 Jurkat 细胞，诱导细胞内 cAMP 水平升高，并显着减少 IL 2 合成。总之，这些结果表明，在 T 淋巴细胞中，前列腺素 E2 受体通过 GTP 结合蛋白与腺苷酸环化酶连接，并通过控制细胞内 cAMP 水平来调节 IL 2 的产生。
T cell activation requires two initial signals that first lead to the expression of interleukin 2 (IL 2) receptors and the initiation of IL 2 synthesis and then to T cell proliferation. Jurkat T lymphoma cells have been shown to be a good model for studying IL 2 synthesis because these cells also require two signals for activation. The first signal can be provided by the lectin phytohaemagglutinin (PHA), and the second one by the phorbol ester, 12-o-tetradecanoylphorbol 13-acetate (TPA). The regulation of IL 2 synthesis in Jurkat cells, however, is unclear, and the present study deals with the role of cAMP on IL 2 synthesis. In Jurkat cells, IL 2 synthesis appears to be highly regulated by the activity of adenylate cyclase. This was demonstrated by using different means to increase intracellular cAMP level, namely by using permeant cAMP analogs, using the activator of adenylate cyclase, forskolin, using the activator of the alpha subunit of the stimulatory GTP binding protein cholera toxin, and using inhibitors of phosphodiesterase. In addition, prostaglandins E1 and E2 were shown to bind specifically to Jurkat cells, to induce a rise in intracellular cAMP level, and to markedly decrease IL 2 synthesis. All together, these results suggest that in T lymphocytes, the prostaglandin E2 receptor is linked to adenylate cyclase through a GTP binding protein and regulates the production of IL 2 by controlling the intracellular cAMP level.