Guan Z, Wu N, Shen Y
Institute of Basic Medical Sciences, CAMS and PUMC, Beijing.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 1996 Apr;18(2):89-94.
Glucocorticoids have wide effects on the immune system, the mechanisms of these effects have not been clearly defined. The interaction of interleukin-2 (IL-2) with its receptor (IL-2R) is a critical control point in the T-cell mediated immune response. The effect of dexamethasone, a synthetic glucocorticoid hormone, on IL-2R is unclear in comparison with its inhibition on the accumulation of IL-2 mRNA. Our study shows that dexamethasone increases the basal and PHA-induced mRNA levels of IL-2R alpha gene in Jurkat cells, but it does not affect the expression of reporter gene constructs containing 5' flanking sequences (-482bp/ +16bp or -350bp/+16bp) of the IL-2R alpha gene in PHA activated Jurkat cells. These results indicate that dexamethasone plays a positive regulatory role in the IL-2R alpha gene expression, but the effect is not mediated by the previously identified proximal regulatory elements located between -482bp/+1bp. Meanwhile, our results also provide evidence that the activation mechanism of dexamethasone is different from that of PHA, and that dexamethasone and PHA show a synergistic effect in the induction of IL-2R alpha gene expression.
糖皮质激素对免疫系统有广泛影响,但其作用机制尚未明确。白细胞介素-2(IL-2)与其受体(IL-2R)的相互作用是T细胞介导的免疫反应中的关键控制点。与地塞米松对IL-2 mRNA积累的抑制作用相比,其对IL-2R的影响尚不清楚。我们的研究表明,地塞米松可增加Jurkat细胞中IL-2Rα基因的基础水平和PHA诱导的mRNA水平,但不影响PHA激活的Jurkat细胞中含有IL-2Rα基因5'侧翼序列(-482bp / +16bp或-350bp / +16bp)的报告基因构建体的表达。这些结果表明,地塞米松在IL-2Rα基因表达中起正调控作用,但该作用不是由先前确定的位于-482bp / +1bp之间的近端调控元件介导的。同时,我们的结果还提供了证据,表明地塞米松的激活机制与PHA不同,并且地塞米松和PHA在诱导IL-2Rα基因表达中显示出协同作用。