Randak C, Brabletz T, Hergenröther M, Sobotta I, Serfling E
Institut für Virologie und Immunbiologie, Universität Würzburg, FRG.
EMBO J. 1990 Aug;9(8):2529-36. doi: 10.1002/j.1460-2075.1990.tb07433.x.
Cyclosporin A (CsA), a powerful immunosuppressive drug, inhibits the synthesis of lymphokines in T lymphocytes at the level of gene transcription. Using protein extracts from El4 lymphoma cells we show that the binding of lymphocyte-specific factors interacting with the two so-called purine boxes (Pu-boxes) of the interleukin 2 (IL-2) enhancer are missing in CsA-treated cells. The CsA-sensitive factors are newly synthesized upon induction. The most prominent factor consists of 45 kd polypeptides and contacts both Pu-boxes at the two central G residues within the identical core sequence AAGAGGAAAA. The CsA-mediated suppression of factor binding to the Pu-boxes correlates well with functional studies in which the inducible, T cell-restricted proto-enhancer activity of Pu-boxes was selectively repressed by CsA. These observations support the conclusion that the suppression of factor binding to the Pu-boxes by CsA impairs the activity of IL-2 and of further lymphokine genes, thereby inhibiting the synthesis of lymphokines in T lymphocytes.
环孢菌素A（CsA）是一种强效免疫抑制药物，它在基因转录水平抑制T淋巴细胞中淋巴因子的合成。利用El4淋巴瘤细胞的蛋白质提取物，我们发现，在经CsA处理的细胞中，与白细胞介素2（IL-2）增强子的两个所谓嘌呤盒（Pu盒）相互作用的淋巴细胞特异性因子的结合缺失。CsA敏感因子在诱导后新合成。最显著的因子由45kd多肽组成，并在相同核心序列AAGAGGAAAA内的两个中央G残基处与两个Pu盒接触。CsA介导的因子与Pu盒结合的抑制与功能研究密切相关，在功能研究中，Pu盒的可诱导、T细胞限制性原增强子活性被CsA选择性抑制。这些观察结果支持这样的结论：CsA对因子与Pu盒结合的抑制损害了IL-2和其他淋巴因子基因的活性，从而抑制了T淋巴细胞中淋巴因子的合成。
