Adenosine inhibits IL-12 and TNF- a production via adenosine A 2a receptor-dependent and independent mechanisms
Adenosine inhibits IL-12 and TNF- a production via adenosine A 2a receptor-dependent and independent mechanisms
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发表时间：
2000
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通讯作者：
G. Haskó;D. Kuhel;Jiang-fan Chen;M. Schwarzschild;E. Deitch;J. Mabley;A. Marton;C. Szabó
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作者：
G. Haskó;D. Kuhel;Jiang-fan Chen;M. Schwarzschild;E. Deitch;J. Mabley;A. Marton;C. Szabó
白细胞介素 12 (IL-12) 是调节 T 辅助细胞 1 与 T 辅助细胞 2 免疫反应的关键细胞因子。在本研究中，我们研究了内源性嘌呤核苷腺苷对 IL-12 产生的影响。在小鼠巨噬细胞中，腺苷抑制 IL-12 的产生。尽管腺苷受体激动剂的效力顺序表明 A 2a 受体参与其中，但从 A 2a 受体缺陷小鼠获得的数据表明，腺苷对 IL-12 甚至 TNF-α 产生的抑制仅部分由 A 2a 受体连接介导。腺苷受体拮抗剂或腺苷摄取阻滞剂双嘧达莫的研究表明，内源性释放的腺苷也会降低 IL-12。尽管腺苷会增加 IL-10 的产生，但对 IL-12 产生的抑制与 IL-10 的增加无关。腺苷的作用机制与 p38 和 p42/p44 丝裂原激活蛋白激酶的激活或 c-Jun 末端激酶的磷酸化的改变无关。腺苷未能影响 IL-12 p35 或 p40 mRNA 的稳态水平，但增加了 IL-10 mRNA 水平。总之，腺苷通过多种腺苷抑制IL-12的产生
Interleukin 12 (IL-12) is a crucial cytokine in the regulation of T helper 1 vs. T helper 2 immune responses. In the present study, we investi-gated the effect of the endogenous purine nucleoside adenosine on the production of IL-12. In mouse macrophages, adenosine suppressed IL-12 production. Although the order of potency of adenosine receptor agonists suggested the involvement of A 2a receptors, data obtained with A 2a receptor-deficient mice showed that the adenosine suppression of IL-12 and even TNF- a production is only partly mediated by A 2a receptor ligation. Studies with adenosine receptor antagonists or the adenosine uptake blocker dipyridamole showed that adenosine released endogenously also decreases IL-12. Although adenosine increases IL-10 production, the inhibition of IL-12 production is independent of the increased IL-10. The mechanism of action of adenosine was not associated with alterations of the activation of the p38 and p42/p44 mitogen-activated protein kinases or the phosphorylation of the c-Jun terminal kinase. Adenosine failed to affect steady-state levels of either IL-12 p35 or p40 mRNA, but augmented IL-10 mRNA levels. In summary, adenosine inhibits IL-12 production via various adenosine