NF-κB synergizes with NF-AT and NF-IL6 in activation of the IL-4 gene in T cells
NF-κB synergizes with NF-AT and NF-IL6 in activation of the IL-4 gene in T cells
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DOI：
10.1002/eji.200324687
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发表时间：
2004-04-01
影响因子：
5.4
通讯作者：
Krammer, PH
中科院分区：
文献类型：
--
作者：
Li-Weber, M;Giaisi, M;Krammer, PH
IL-4在Th2细胞介导的体液免疫反应中起关键作用，并可引起IgE依赖型变态反应性炎症性疾病。IL-4在分化的Th2细胞中的表达受转录因子如核因子-AT、AP-1和核因子-IL-6的调节。近年来，越来越多的证据表明，促炎转录因子NF-kappaB，13也可能参与了IL-4的表达。在本研究中，我们证明了在NF-kappaB/NF-AT/NF-IL6复合位点上，NF-kappaB、NF-AT和NF-IL6协同激活了IL-4启动子。此外，我们还进行了染色质免疫沉淀技术，以确定核因子-kappaB在体内IL-4基因激活中的功能相关性。我们证明，核因子-kappaB在体内结合到T细胞激活后的IL-4启动子上。抑制活细胞中的核因子-kappaB核转位可阻断核因子-kappaB与IL-4启动子的结合。这些数据首次提供了核因子-kappaB直接参与IL-4转录的证据。
IL-4 plays a pivotal role in the development of the Th2 cell mediated humoral immune response and causes IgE-dependent allergic inflammatory diseases. Expression of IL-4 in differentiated Th2 cells is regulated by transcription factors such as NF-AT AP-1 and NF-IL6. Recently, increasing evidence indicates that the pro-inflammatory transcription factor NF-kappaB,13 may also participate in IL-4 expression. In this study, we show that the IL-4 promoter is synergistically activated by NF-kappaB, NF-AT and NF-IL6 at the NF-kappaB/NF-AT/NF-IL6 composite sites. In addition, we performed the chromatin immunoprecipitation technique to determine the functional relevance of NF-kappaB in the activation of the IL-4 gene in vivo. We demonstrate that NF-kappaB binds to the IL-4 promoter in vivo upon T cell activation. Inhibition of NF-kappaB nuclear translocation in living cells blocked binding of NF-kappaB to the IL-4 promoter. The data provide first evidence that NF-kappaB is directly involved in IL-4 transcription.