NF-kappa B synergizes with NF-AT and NF-IL6 in activation of the IL-4 gene in T cells.

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.