抗糖皮质激素RU486可下调正常人淋巴细胞中白细胞介素-2受体的表达。

The antiglucocorticoid RU486 downregulates the expression of interleukin-2 receptors in normal human lymphocytes.

作者信息

Antonakis N, Markogiannakis E, Theodoropoulou M, Georgoulias V, Stournaras C, Gravanis A

机构信息

Department of Basic Sciences, School of Medicine, University of Crete, Iraklion, Greece.

出版信息

J Steroid Biochem Mol Biol. 1991 Dec;39(6):929-35. doi: 10.1016/0960-0760(91)90351-5.

DOI:10.1016/0960-0760(91)90351-5

PMID:1751392

Abstract

The effects of the antiglucocorticoid RU486 on the expression of low and high affinity interleukin-2 receptors (IL-2R) in phytohaemagglutinin (PHA)-activated human peripheral blood lymphocytes were investigated. We demonstrated that RU486 inhibits in a dose-dependent way the expression of both classes of IL-2R, thereby mimicking the effects of the glucocorticoid agonist dexamethasone. The maximal effect on the low affinity binding sites was observed at 10 microM (28 +/- 2% of control, P less than 0.001) and on the high affinity IL-2R at 1 microM (from 2938 +/- 74 to 437 +/- 108 binding sites per cell, P less than 0.001). This inhibition of IL-2R expression occurs at a pretranslational level since RU486 decreased the accumulation of beta-chain IL-2R mRNA transcripts. Our data support the concept that the antiglucocorticoid RU486 at pharmacological concentrations can exert agonistic-immunosuppressive effects.

摘要

研究了抗糖皮质激素RU486对植物血凝素（PHA）激活的人外周血淋巴细胞中低亲和力和高亲和力白细胞介素-2受体（IL-2R）表达的影响。我们证明，RU486以剂量依赖的方式抑制两类IL-2R的表达，从而模拟糖皮质激素激动剂地塞米松的作用。在10微摩尔时观察到对低亲和力结合位点的最大影响（为对照的28±2%，P<0.001），在1微摩尔时对高亲和力IL-2R的最大影响（从每细胞2938±74个结合位点降至437±108个结合位点，P<0.001）。由于RU486降低了β链IL-2R mRNA转录本的积累，这种对IL-2R表达的抑制发生在翻译前水平。我们的数据支持这样一种观点，即药理浓度的抗糖皮质激素RU486可发挥激动剂免疫抑制作用。