Almawi W Y, Beyhum H N, Rahme A A, Rieder M J
Department of Biochemistry, Faculty of Medicine, American University of Beirut, Lebanon.
J Leukoc Biol. 1996 Nov;60(5):563-72. doi: 10.1002/jlb.60.5.563.
Glucocorticoids (GCS) profoundly inhibit several aspects of T cell immunity largely through inhibition of cytokine expression at the transcriptional and posttranscriptional levels. GCS were also reported to act indirectly by inducing transforming growth factor-beta expression, which in turn blocks T cell immunity. In exerting their antiproliferative effects, GCS diffuse into target cells where they bind their cytoplasmic receptor, which in turn translocates to the nucleus where it inhibits transcription of cytokine genes through direct binding to the glucocorticoid response elements (GRE), which are located in the promoter region of cytokine genes or, alternatively, through antagonism of the action of transcription factors required for optimal transcriptional activation. In contrast to their inhibitory effects on cytokine expression, GCS up-regulate cytokine receptor expression that correlates with enhanced cytokine effects on target cells. In this review, we summarize the current state of knowledge of the mechanism of action of GCS, including the phenomenon of steroid-induced rebound, which ensues upon GCS withdrawal.
糖皮质激素（GCS）在很大程度上通过在转录和转录后水平抑制细胞因子表达，从而深刻抑制T细胞免疫的多个方面。据报道，GCS还通过诱导转化生长因子-β表达间接发挥作用，进而阻断T细胞免疫。在发挥其抗增殖作用时，GCS扩散到靶细胞中，与细胞质受体结合，该受体进而转运至细胞核，在细胞核中通过直接结合位于细胞因子基因启动子区域的糖皮质激素反应元件（GRE），或者通过拮抗最佳转录激活所需转录因子的作用，来抑制细胞因子基因的转录。与它们对细胞因子表达的抑制作用相反，GCS上调细胞因子受体表达，这与细胞因子对靶细胞增强的作用相关。在本综述中，我们总结了目前关于GCS作用机制的知识现状，包括GCS撤药后出现的类固醇诱导的反弹现象。
