DIFFERENTIAL EFFECT OF CYCLOSPORINE-A ON ACTIVATION SIGNALING IN HUMAN T-CELL LINES
DIFFERENTIAL EFFECT OF CYCLOSPORINE-A ON ACTIVATION SIGNALING IN HUMAN T-CELL LINES
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DOI：
10.1172/jci112464
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发表时间：
1986-05-01
影响因子：
15.9
通讯作者：
STOBO, JD
中科院分区：
文献类型：
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作者：
MANGER, B;HARDY, KJ;STOBO, JD
利用体外可诱导分泌白细胞介素2（IL-2）的不同T细胞系，研究环孢素A（CsA）对IL-2分泌的影响。T白血病细胞Jurkat需要胞浆钙浓度（[Ca++]i）和佛波醇肉豆蔻酸酯（PMA）的增加来诱导IL-2的产生，这被CsA完全阻断。另一种T细胞系HUT 78也响应于[Ca++]i和PMA的升高而产生IL-2;然而，在HUT 78中，PMA也诱导不被CsA阻断的低水平的IL-2产生。用5-氮胞苷处理后，HUT 78细胞产生最大水平的IL-2，以响应单独的PMA，而不需要[Ca++]i增加刺激。在这些细胞中，CsA对PMA诱导的活化没有抑制作用。此外，CsA不抑制PMA诱导的蛋白激酶C易位。这些数据表明，CsA不全面抑制IL-2基因表达，而是干扰T细胞活化的信号转导事件。
Different T cell lines, which can be induced to secrete interleukin 2 (IL-2) in vitro, were used to dissect the effect of cyclosporin A (CsA). The T leukemia cell Jurkat requires an increase in cytoplasmic calcium concentration ([Ca++]i) and phorbol myristate acetate (PMA) for the induction of IL-2 production, which is completely blocked by CsA. Another T cell line, HUT 78, also produces IL-2 in response to a rise in [Ca++]i and PMA; however, in HUT 78, PMA also induces low levels of IL-2 production that is not blocked by CsA. After treatment with 5-azacytidine, HUT 78 cells produced maximal levels of IL-2 in response to PMA alone without requiring [Ca++]i increasing stimuli. In these cells no inhibitory effect of CsA on PMA-induced activation could be demonstrated. In addition, CsA does not inhibit PMA-induced translocation of protein kinase C. These data suggest that CsA does not globally inhibit IL-2 gene expression, but rather interferes with signaling events of T cell activation.