Lewis G M, Caccese R G, Heaslip R J, Bansbach C C
Wyeth-Ayerst Research, Princeton, NJ 08453.
Agents Actions. 1993;39 Spec No:C89-92. doi: 10.1007/BF01972730.
Interleukin-2 (IL-2) is a major mediator of immunologic responses involved in many chronic inflammatory diseases. We have investigated the effects of rolipram, a PDE-IV inhibitor, and CI-930, a PDE-III inhibitor, on IL-2 gene expression in the Jurkat human T cell line. The immunosuppressant cyclosporin A (CsA) was included as a positive control. Jurkat cells were stimulated with 1 microgram/ml phytohemagglutinin (PHA) and 50 ng/ml phorbol 12-myristate, 13-acetate (PMA) for 6 h, and mRNA was analyzed using reverse transcription and polymerase chain reaction (RT/PCR). IL-2 transcription was greatly inhibited by 1 microM CsA, whereas neither 10 microM rolipram nor 10 microM CI-930 had any effect on steady-state levels of IL-2 mRNA. Therefore, PDE inhibitors do not affect synthesis of IL-2 mRNA in this model of activated T cells. This is of interest given that these agents inhibit the proliferation of primary T cells. For murine splenocytes stimulated by 2.5 micrograms/ml concanavalin A (Con A), rolipram had an IC50 of 0.09 microM and CI-930 an IC50 of 4.4 microM. These concentrations are below those at which IL-2 mRNA synthesis was shown to be unaffected. Therefore, the mechanism by which inhibitors of PDE-III and PDE-IV affect T cell proliferation is not likely to involve suppression of IL-2 mRNA transcription.
白细胞介素-2（IL-2）是参与多种慢性炎症性疾病的免疫反应的主要介质。我们研究了磷酸二酯酶-4（PDE-IV）抑制剂咯利普兰和磷酸二酯酶-3（PDE-III）抑制剂CI-930对Jurkat人T细胞系中IL-2基因表达的影响。免疫抑制剂环孢素A（CsA）作为阳性对照。用1微克/毫升植物血凝素（PHA）和50纳克/毫升佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）刺激Jurkat细胞6小时，使用逆转录和聚合酶链反应（RT/PCR）分析mRNA。1微摩尔/升的CsA可显著抑制IL-2转录，而10微摩尔/升的咯利普兰和10微摩尔/升的CI-930对IL-2 mRNA的稳态水平均无影响。因此，在这种活化T细胞模型中，PDE抑制剂不影响IL-2 mRNA的合成。鉴于这些药物可抑制原代T细胞的增殖，这一点很有意思。对于用2.5微克/毫升刀豆蛋白A（Con A）刺激的小鼠脾细胞，咯利普兰的半数抑制浓度（IC50）为0.09微摩尔/升，CI-930的IC50为4.4微摩尔/升。这些浓度低于显示对IL-2 mRNA合成无影响的浓度。因此，PDE-III和PDE-IV抑制剂影响T细胞增殖的机制不太可能涉及抑制IL-2 mRNA转录。
