Vint I A, Chain B M, Foreman J C
Department of Pharmacology, University College London, UK.
Agents Actions. 1993 Nov;40(3-4):209-14. doi: 10.1007/BF01984063.
Auranofin, 30-300 nM causes a concentration-dependent potentiation of phytohaemagglutinin (PHA)-induced interleukin-2 (IL-2) release from human peripheral blood mononuclear cells in culture. At concentrations of auranofin between 1 and 3 microM, PHA-stimulated IL-2 release was inhibited, and the drug is cytotoxic at these concentrations. At concentrations of auranofin which potentiated PHA-induced IL-2 release, it had no effect on [3H]-thymidine incorporation. Auranofin, 3 to 300 nM caused a concentration-dependent increase in the population of peripheral blood mononuclear cells bearing the IL-2 receptor (Tac positive cells). Auranofin, 300 nM caused an increase of approximately 100% in the glutathione level within the resting cells, and also increased the glutathione level in PHA-stimulated cells. We conclude that auranofin acts early in the cell cycle, selectively to increase the release of IL-2 and the expression of Tac. The action of auranofin on cellular glutathione levels may alter the redox state of the cell which is known to be important in the control of transcription factor activation.
金诺芬，30 - 300纳摩尔可引起培养的人外周血单个核细胞中植物血凝素（PHA）诱导的白细胞介素-2（IL-2）释放呈浓度依赖性增强。在金诺芬浓度为1至3微摩尔时，PHA刺激的IL-2释放受到抑制，且该药物在这些浓度下具有细胞毒性。在能增强PHA诱导的IL-2释放的金诺芬浓度下，它对[3H] - 胸腺嘧啶核苷掺入没有影响。3至300纳摩尔的金诺芬可使携带IL-2受体的外周血单个核细胞群体（Tac阳性细胞）呈浓度依赖性增加。300纳摩尔的金诺芬使静息细胞内谷胱甘肽水平增加约100%，并且也增加了PHA刺激细胞内的谷胱甘肽水平。我们得出结论，金诺芬在细胞周期早期起作用，选择性地增加IL-2的释放和Tac的表达。金诺芬对细胞谷胱甘肽水平的作用可能会改变细胞的氧化还原状态，而氧化还原状态已知在转录因子激活的控制中很重要。
