c-rel regulation of IL-2 gene expression may be mediated through activation of AP-1.
c-rel regulation of IL-2 gene expression may be mediated through activation of AP-1.
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DOI：
10.1084/jem.184.5.1663
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发表时间：
1996-11-01
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通过抗原/MHC的T细胞活化诱导对免疫应答至关重要的几种基因的表达，包括白细胞介素-2。来自NF-κ B家族成员c-rel缺陷小鼠的T细胞不能激活IL-2基因表达。然而，突变IL-2启动子中的NF-κ B位点仅具有中等影响。为了研究c-Rel可以调节IL-2基因表达的其他方式，我们确定了c-Rel过表达是否可以增加参与IL-2启动子调节的其他转录因子的活性：NF-AT、Oct/OAP（ARRE-1）和AP-1。在Jurkat TAg细胞中，c-Rel的过表达使AP-1活化增加约17倍。此外，由抗TCR Ab或PMA/离子霉素刺激的AP-1活性通过c-Rel过表达进一步增加。c-Rel过表达不影响NF-AT或ARRE-1活性。此外，c-Rel的过表达激活了IL-2启动子（NF-IL-2B）的非共有AP-1位点，尽管程度较低，约为6倍。AP-1的激活需要c-Rel的DNA结合和反式激活结构域。我们的研究结果可能为c-rel缺陷小鼠IL-2基因激活的影响提供了解释。
T cell activation by antigen/MHC induces the expression of several genes critical to the immune response, including interleukin-2. T cells from mice deficient for the NF-kappa B family member c-rel cannot activate IL-2 gene expression. However, mutating the NF-kappa B site in the IL-2 promoter has only moderate effects. To investigate additional ways c-Rel could regulate IL-2 gene expression, we determined whether c- rel overexpression could increase the activity of other transcription factors involved in IL-2 promoter regulation: NF-AT, Oct/OAP (ARRE-1), and AP-1. In Jurkat TAg cells, overexpression of c-Rel increased AP-1 activation approximately 17-fold. Moreover, AP-1 activity stimulated by anti-TCR Abs or PMA/ionomycin was further increased by c-Rel overexpression. c-Rel overexpression did not affect NF-AT or ARRE-1 activity. Additionally, overexpression of c-Rel activated the nonconsensus AP-1 site from the IL-2 promoter (NF-IL-2B), although to a lesser extent, approximately sixfold. AP-1 activation required both the DNA binding and transactivation domains of c-Rel. Our results may provide an explanation for the effect on IL-2 gene activation in c-rel- deficient mice.