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.
Li-Weber
Min
M
Tumor Immunology Program, German Cancer Research Center (DKFZ), Heidelberg, Germany. m.li-weber@dkfz-heidelberg.de
Giaisi
Marco
M
Baumann
Sven
S
Pálfi
Katalin
K
Krammer
Peter H
PH
D005786:Gene Expression Regulation; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics* / Q000276:immunology; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology*; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018418:Th2 Cells / Q000276:immunology*; D014157:Transcription Factors / Q000276:immunology*; D014158:Transcription, Genetic; D014162:Transfection
D016328:NF-kappa B; D012333:RNA, Messenger; D014157:Transcription Factors; D015847:Interleukin-4