Ryffel B, Willcocks J L, Brooks N, Woerly G
Institute of Toxicology, University of Zürich, Schwerzenbach, Switzerland.
Immunopharmacology. 1995 Sep;30(3):199-207. doi: 10.1016/0162-3109(95)00023-m.
We investigated the transcription and expression of the interleukin-2 receptor (IL-2R, CD25) in human T-lymphocytes after different modes of T-lymphocyte stimulation in the presence of the immunosuppressants cyclosporin (CsA) and tacrolimus (FK506) as well as the structurally related macrolide rapamycin. We demonstrate that CsA and FK506 inhibited IL-2R (CD25) gene transcription and protein expression after stimulation by anti-CD3 or ionomycin, but not by phorbol ester or IL-2. Rapamycin, which does not affect IL-2 transcription, surprisingly inhibited IL-2R upregulation after anti-CD3- or ionomycin-induced stimulation, but not by phorbol ester or IL-2. Interestingly, the protein synthesis inhibitor anisomycin inhibited anti-CD3- or ionomycin-, but not phorbol ester- and IL-2-induced CD25 gene transcription indicating the dependence on de novo protein synthesis of the former pathways. These data suggest that the pharmacological effect of the imunosuppressants tested on IL-2R gene expression may be predicted by the requirement of protein synthesis of a given activation pathway.
我们研究了在免疫抑制剂环孢素（CsA）、他克莫司（FK506）以及结构相关的大环内酯类药物雷帕霉素存在的情况下，不同模式刺激人T淋巴细胞后白细胞介素-2受体（IL-2R，CD25）的转录和表达。我们证明，CsA和FK506在抗CD3或离子霉素刺激后可抑制IL-2R（CD25）基因转录和蛋白表达，但在佛波酯或IL-2刺激后则无此作用。雷帕霉素不影响IL-2转录，令人惊讶的是，它在抗CD3或离子霉素诱导的刺激后可抑制IL-2R上调，但在佛波酯或IL-2刺激后则无此作用。有趣的是，蛋白质合成抑制剂茴香霉素可抑制抗CD3或离子霉素诱导的，但不抑制佛波酯和IL-2诱导的CD25基因转录，这表明前一种途径依赖于从头合成蛋白质。这些数据表明，所测试的免疫抑制剂对IL-2R基因表达的药理作用可能通过特定激活途径对蛋白质合成的需求来预测。
