NF‐κB synergizes with NF‐AT and NF‐IL6 in activation of the IL‐4 gene in T cells

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Abstract
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‐κB may also participate inIL‐4 expression. In this study, we show that the IL‐4 promoter is synergistically activated by NF‐κB, NF‐AT and NF‐IL6 at the NF‐κB/NF‐AT/NF‐IL6 composite sites. In addition, we performed the chromatin immunoprecipitation technique to determine the functional relevance of NF‐κB in the activation of the IL‐4 gene in vivo. We demonstrate that NF‐κB binds to the IL‐4 promoter in vivo upon T cell activation. Inhibition of NF‐κB nuclear translocation in living cells blocked binding of NF‐κB to the IL‐4 promoter. The data provide first evidence that NF‐κB is directly involved in IL‐4 transcription.