title: Early growth response protein-1 (Egr-1) is preferentially expressed in T helper type 2 (Th2) cells and is involved in acute transcription of the Th2 cytokine interleukin-4.
abstract: The early growth response gene product Egr-1 has been shown to have great impact on growth, proliferation, and differentiation in a wide variety of cells, including T cells. In this study, we show that Egr-1 is rapidly induced upon T cell stimulation and is expressed predominantly in T helper type 2 (Th2) compared with type 1 (Th1) cells. We further investigate the role of Egr-1 in regulation of the Th2 cytokine interleukin-4 (IL-4) expression. IL-4 is a key Th2 cytokine that regulates humoral immunity and also causes allergic inflammation. Regulation of IL-4 gene transcription in Th2 cells has been shown to be controlled by multiple T cell receptor (TCR)-induced transcription factors. However, only a few transcription factors were shown to be selectively induced in differentiated Th2 cells in response to TCR stimulation. Chromatin immunoprecipitation analysis demonstrates that Egr-1 binds to the IL-4 promoter in vivo upon T cell stimulation. Ectopic expression of Egr-1 enhances endogenous IL-4 mRNA expression and elevates IL-4 promoter activity. We also show that Egr-1, nuclear factor of activated T cell, and NF-kappaB cooperatively bind to an NFAT/NF-kappaB-overlapping IL-4 enhancer element and activate the IL-4 promoter synergistically. Furthermore, we show that antisense oligonucleotides that knock down Egr-1 expression attenuate IL-4 transcription. Our study provides the first evidence that Egr-1 protein is differentially expressed in Th1 and Th2 cells and is involved in the acute phase of the IL-4 transcription in response to TCR stimulation.
authors.affiliation: Tumor Immunology Program D030, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Lohoff
authors.forename: Marco
authors.initials: M
authors.lastname: Giaisi
authors.forename: Rebecca
authors.initials: R
authors.lastname: Köhler
authors.forename: Bärbel
authors.initials: B
authors.lastname: Casper
authors.forename: Peter H
authors.initials: PH
authors.lastname: Krammer
authors.forename: Min
authors.initials: M
authors.lastname: Li-Weber
mesh_terms: D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D002460:Cell Line; D015536:Down-Regulation; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000378:metabolism*; D018418:Th2 Cells / Q000166:cytology / Q000378:metabolism*; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D051766:Early Growth Response Protein 1; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4