Effects of prostaglandin E2 on Th0-type human T cell clones: modulation of functions of nuclear proteins involved in cytokine production.
Effects of prostaglandin E2 on Th0-type human T cell clones: modulation of functions of nuclear proteins involved in cytokine production.
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前列腺素 E2 对 Th0 型人类 T 细胞克隆的影响：调节参与细胞因子产生的核蛋白的功能。
DOI：
10.1093/intimm/6.4.523
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发表时间：
1994
影响因子：
4.4
通讯作者：
Ken‐ichi Arai
中科院分区：
文献类型：
--
作者：
Sumiko Watanabe;H. Yssel;Yoshio Harada;Ken‐ichi Arai
研究了前列腺素E2（PGE 2）对CD 4+人辅助性T细胞克隆SP-B21细胞因子产生和增殖的影响。在用抗CD 3 mAb刺激的细胞中，PGE 2抑制细胞增殖和检测的所有细胞因子的产生。rIL-2的加入完全恢复了增殖反应，并部分恢复了IL-4和IL-5的产生，但不能恢复其他细胞因子的产生。相反，在用佛波醇肉豆蔻酸酯乙酸酯（PMA）/A23187刺激的细胞中，PGE 2增强IL-4和IL-5的产生，并且仅部分抑制其它细胞因子的产生。因此，PGE 2的作用根据T细胞活化的模式而变化，并且IL-4和IL-5的调节与其他细胞因子不同。在迁移率变动分析中，在未刺激的SP-B21细胞中，在与κ B序列形成的复合物中仅观察到NF-κ B（p50/p50）同源二聚体。当用抗CD 3 mAb或PMA/A23187刺激细胞时，诱导NF-κ B（p50/p65）异源二聚体与κ B序列形成复合物。有趣的是，PGE 2或二丁酰（Bt 2）cAMP消除了NF-κ B（p50/p65）异源二聚体与kappa B序列在抗CD 3单克隆抗体刺激的细胞中的结合，而不是PMA/A23187。我们的研究结果表明，PGE 2作用的靶点是导致蛋白激酶C活化的信号转导途径中的一个组分。然而，PGE 2对T细胞活化信号的抑制是选择性的。当细胞被抗CD 3单抗或PMA/A23187刺激激活时，PGE 2增强了与NF-AT、AP-1和CLE 0序列的复合物形成。因此，似乎PGE 2通过升高cAMP水平而干扰NF-κ B的活化途径，但不干扰NF-AT、AP-1或CLE 0结合蛋白的活化途径。
The effects of prostaglandin E2 (PGE2) on cytokine production and proliferation of the CD4+ human helper T cell clone SP-B21 were investigated. In cells stimulated with anti-CD3 mAb, PGE2 inhibited cell proliferation and the production of all the cytokines examined. Addition of rIL-2 fully restored the proliferative response and partially restored the production of IL-4 and IL-5, but not that of other cytokines. In contrast, in cells stimulated with phorbol myristate acetate (PMA)/A23187, PGE2 enhanced the production of IL-4 and IL-5, and only partially inhibited the production of other cytokines. Therefore, the effects of PGE2 vary depending on the mode of T cell activation, and the IL-4 and IL-5 are regulated differently from other cytokines. In a mobility shift assay, only the NF-kappa B (p50/p50) homodimer was observed in a complex formed with the kappa B sequence in unstimulated SP-B21 cells. When cells were stimulated with anti-CD3 mAb or PMA/A23187, a complex formation of NF-kappa B (p50/p65) heterodimer with the kappa B sequence was induced. Interestingly, PGE2 or di-butyryl (Bt2)cAMP abolished the binding of NF-kappa B (p50/p65) heterodimer to the kappa B sequence in cells stimulated with anti-CD3 mAb but not with PMA/A23187. Our results suggest that the target of PGE2 action is a component in the signal transduction pathway leading to the activation of protein kinase C. However, the inhibition of the T cell activation signals by PGE2 is selective. PGE2 enhanced the complex formation with NF-AT, AP-1 and CLE0 sequences when the cells were activated by either anti-CD3 mAb or PMA/A23187 stimulation. It seems therefore that PGE2, by elevating cAMP levels, interferes with the activation pathway for NF-kappa B but not for NF-AT, AP-1 or CLE0 binding protein.