Zhang D H, Yang L, Ray A
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
J Immunol. 1998 Oct 15;161(8):3817-21.
The cytokines IL-4 and IL-5 are often coordinately produced by Th2 cells as in asthma. However, it is unclear whether similar molecular mechanisms underlie transcription of the two genes. We have previously shown that the transcription factor GATA-3 is expressed in Th2 but not Th1 cells and is crucial for activation of the IL-5 promoter by different stimuli. In a different study, GATA-3 was shown to be sufficient for the expression of IL-4 and other Th2 cytokine genes. Here, we show that ectopic expression of GATA-3 is sufficient to drive IL-5 but not IL-4 gene expression. Also, in Th2 cells, antisense GATA-3 RNA inhibits IL-5 but not IL-4 promoter activation. The induction of IL-5 gene expression by GATA-3 involves high affinity binding of GATA-3 to an inverted GATA repeat in the IL-5 promoter.
细胞因子白细胞介素-4（IL-4）和白细胞介素-5（IL-5）通常如在哮喘中那样由辅助性T细胞2（Th2细胞）协同产生。然而，尚不清楚这两个基因转录的背后是否存在相似的分子机制。我们之前已表明转录因子GATA-3在Th2细胞而非Th1细胞中表达，并且对于不同刺激激活IL-5启动子至关重要。在另一项研究中，GATA-3被证明足以驱动IL-4和其他Th2细胞因子基因的表达。在此，我们表明GATA-3的异位表达足以驱动IL-5而非IL-4基因的表达。此外，在Th2细胞中，反义GATA-3 RNA抑制IL-5而非IL-4启动子的激活。GATA-3对IL-5基因表达的诱导涉及GATA-3与IL-5启动子中反向GATA重复序列的高亲和力结合。
