Li-Weber Min, Giaisi Marco, Baumann Sven, Pálfi Katalin, Krammer Peter H
Tumor Immunology Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Eur J Immunol. 2004 Apr;34(4):1111-8. doi: 10.1002/eji.200324687.
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-kappa B may also participate inIL-4 expression. In this study, we show that the IL-4 promoter is synergistically activated by NF-kappa B, NF-AT and NF-IL6 at the NF-kappa B/NF-AT/NF-IL6 composite sites. In addition, we performed the chromatin immunoprecipitation technique to determine the functional relevance of NF-kappa B in the activation of the IL-4 gene in vivo. We demonstrate that NF-kappa B binds to the IL-4 promoter in vivo upon T cell activation. Inhibition of NF-kappa B nuclear translocation in living cells blocked binding of NF-kappa B to the IL-4 promoter. The data provide first evidence that NF-kappa B is directly involved in IL-4 transcription.
白细胞介素-4在Th2细胞介导的体液免疫反应的发展中起关键作用，并引发依赖于免疫球蛋白E的过敏性炎症疾病。分化的Th2细胞中白细胞介素-4的表达受转录因子如活化T细胞核因子、激活蛋白-1和核因子白细胞介素-6的调控。最近，越来越多的证据表明促炎转录因子核因子κB也可能参与白细胞介素-4的表达。在本研究中，我们表明白细胞介素-4启动子在核因子κB/活化T细胞核因子/核因子白细胞介素-6复合位点被核因子κB、活化T细胞核因子和核因子白细胞介素-6协同激活。此外，我们进行了染色质免疫沉淀技术以确定核因子κB在体内白细胞介素-4基因激活中的功能相关性。我们证明T细胞活化后核因子κB在体内与白细胞介素-4启动子结合。抑制活细胞中核因子κB的核转位可阻止核因子κB与白细胞介素-4启动子的结合。这些数据首次证明核因子κB直接参与白细胞介素-4的转录。
