Manger B, Hardy K J, Weiss A, Stobo J D
J Clin Invest. 1986 May;77(5):1501-6. doi: 10.1172/JCI112464.
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 alone 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.
不同的T细胞系，它们在体外可被诱导分泌白细胞介素2（IL-2），被用于剖析环孢菌素A（CsA）的作用。T白血病细胞Jurkat需要细胞质钙浓度（[Ca++]i）升高以及佛波酯（PMA）来诱导IL-2的产生，而这一过程完全被CsA阻断。另一个T细胞系HUT 78，同样会响应[Ca++]i升高和PMA产生IL-2；然而，在HUT 78中，单独的PMA可诱导产生低水平的IL-2，且不受CsA的阻断。用5-氮杂胞苷处理后，HUT 78细胞仅对PMA产生最大水平的IL-2，而无需[Ca++]i升高刺激。在这些细胞中，未证实CsA对PMA诱导的激活有抑制作用。此外，CsA不抑制PMA诱导的蛋白激酶C易位。这些数据表明，CsA并非全面抑制IL-2基因表达，而是干扰T细胞激活的信号事件。
