C/EBPbeta enhances IL-4 but impairs IL-2 and IFN-gamma induction in T cells
- PMID: 11009091
- DOI: 10.1002/1521-4141(200009)30:9<2576::AID-IMMU2576>3.0.CO;2-N
C/EBPbeta enhances IL-4 but impairs IL-2 and IFN-gamma induction in T cells
Abstract
C/EBP transcription factors have been described to control the activity of the human IL-4 promoter. The C/EBP binding sites within the IL-4 promoter overlap with composite NF-AT and AP-1 binding motifs. We show here that similar binding sites are part of the murine IL-4 promoter. Retroviral overexpression of C/EBPbeta in murine EL-4 thymoma cells led to a strong induction of endogenous IL-4 and a reduction in IL-2 and IFN-gamma expression. Similarily, in primary murine T cells C/EBPbeta induction resulted in an increase in IL-4 levels, whereas in human Jurkat T cells a decrease in IL-2 RNA was detected. Like AP-1, C/EBP factors belong to the large class of basic leucine zipper proteins. However, unlike AP-1, C/EBPbeta does not act in synergy with NF-AT in the induction of the murine IL-4 promoter. Instead, both factors compete in their binding to the P4/Pu-bD site, one of the most important sequence elements of the IL-4 promoter. Whereas NF-AT factors require high levels of free Ca2+ and calcineurin activity for induction, C/EBP induction in T cells is Ca2+/calcineurin independent. These observations suggest that various induction conditions lead to the activation of transcription factors, inducing IL-4 promoter activity at specific developmental stages of T cells.
Similar articles
-
Octamer factors exert a dual effect on the IL-2 and IL-4 promoters.J Immunol. 1994 Dec 15;153(12):5572-85. J Immunol. 1994. PMID: 7989759
-
Th2-specific protein/DNA interactions at the proximal nuclear factor-AT site contribute to the functional activity of the human IL-4 promoter.J Immunol. 1998 Aug 1;161(3):1380-9. J Immunol. 1998. PMID: 9686601
-
Nuclear factor-IL6 activates the human IL-4 promoter in T cells.J Immunol. 1995 Dec 1;155(11):5273-9. J Immunol. 1995. PMID: 7594540
-
NF-Y, IRF-2, and C/EBP proteins are involved in regulation of human IL-4 gene expression.Immunobiology. 1995 Jul;193(2-4):263-7. doi: 10.1016/S0171-2985(11)80553-X. Immunobiology. 1995. PMID: 8530153 Review. No abstract available.
-
[Critical roles of the CCAAT/enhancer-binding protein family].Tanpakushitsu Kakusan Koso. 2000 Jun;45(9 Suppl):1577-84. Tanpakushitsu Kakusan Koso. 2000. PMID: 10879137 Review. Japanese. No abstract available.
Cited by
-
Hydroquinone, a reactive metabolite of benzene, enhances interleukin-4 production in CD4+ T cells and increases immunoglobulin E levels in antigen-primed mice.Immunology. 2002 Aug;106(4):496-502. doi: 10.1046/j.1365-2567.2002.01451.x. Immunology. 2002. PMID: 12153512 Free PMC article.
-
NFATc1 supports imiquimod-induced skin inflammation by suppressing IL-10 synthesis in B cells.Nat Commun. 2016 May 25;7:11724. doi: 10.1038/ncomms11724. Nat Commun. 2016. PMID: 27222343 Free PMC article.
-
Impaired CD4+ T-cell proliferation and effector function correlates with repressive histone methylation events in a mouse model of severe sepsis.Eur J Immunol. 2010 Apr;40(4):998-1010. doi: 10.1002/eji.200939739. Eur J Immunol. 2010. PMID: 20127677 Free PMC article.
-
Adaptation of hepatitis C virus to mouse CD81 permits infection of mouse cells in the absence of human entry factors.PLoS Pathog. 2010 Jul 1;6(7):e1000978. doi: 10.1371/journal.ppat.1000978. PLoS Pathog. 2010. PMID: 20617177 Free PMC article.
-
T-bet antagonizes mSin3a recruitment and transactivates a fully methylated IFN-gamma promoter via a conserved T-box half-site.Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):2034-9. doi: 10.1073/pnas.0409510102. Epub 2005 Jan 31. Proc Natl Acad Sci U S A. 2005. PMID: 15684083 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous
