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Nucleic Acids Res
2003 Dec 01;3123:6722-32. doi: 10.1093/nar/gkg861.
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Interleukin-6 represses the transcription of the CCAAT/enhancer binding protein-alpha gene in hepatoma cells by inhibiting its ability to autoactivate the proximal promoter region.
Foka P
,
Irvine SA
,
Kockar F
,
Ramji DP
.
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The cytokine interleukin-6 (IL-6) plays key roles in the immune and inflammatory responses, acute-phase reaction and hematopoiesis. Such biological actions of IL-6 are characterised by both the activation and the inhibition of gene transcription. Unfortunately, in contrast to gene activation, the mechanism by which IL-6 suppresses transcription remains largely unclear. We have, therefore, investigated this aspect using the Xenopus laevis CCAAT/enhancer binding protein-alpha (C/EBPalpha) gene promoter as a model. We show by transient transfection assays of various promoter-luciferase DNA constructs into hepatoma cells that a C/EBP recognition sequence in the proximal promoter region is essential for the IL-6-mediated repression. Electrophoretic mobility shift assays showed that C/EBPalpha was the major protein that bound to this site and, consistent with its expression pattern, the binding was reduced when the cells were exposed to IL-6. Co-transfection assays revealed for the first time that the ability of C/EBPalpha, but not C/EBPbeta or Sp1, to transactivate the promoter was decreased dramatically when the cells were incubated with IL-6. These studies, therefore, identify a novel mechanism for IL-6-mediated repression of gene transcription that involves a reduction in C/EBPalpha-mediated activation.
Akira,
IL-6-regulated transcription factors.
1997,
Pubmed
Akira,
NF-IL6 and NF-kappa B in cytokine gene regulation.
1997,
Pubmed
Alam,
Differential expression of three C/EBP isoforms in multiple tissues during the acute phase response.
1992,
Pubmed
Antonson,
Myc inhibits CCAAT/enhancer-binding protein alpha-gene expression in HIB-1B hibernoma cells through interactions with the core promoter region.
1995,
Pubmed
Baer,
Generation of truncated C/EBPbeta isoforms by in vitro proteolysis.
2000,
Pubmed
Bode,
LPS and TNFalpha induce SOCS3 mRNA and inhibit IL-6-induced activation of STAT3 in macrophages.
1999,
Pubmed
Calkhoven,
Multiple steps in the regulation of transcription-factor level and activity.
1996,
Pubmed
Christy,
CCAAT/enhancer binding protein gene promoter: binding of nuclear factors during differentiation of 3T3-L1 preadipocytes.
1991,
Pubmed
Citarella,
Interleukin-6 downregulates factor XII production by human hepatoma cell line (HepG2).
1997,
Pubmed
Davies,
The ovine CCAAT-enhancer binding protein delta gene: cloning, characterization, and species-specific autoregulation.
2000,
Pubmed
Descombes,
A liver-enriched transcriptional activator protein, LAP, and a transcriptional inhibitory protein, LIP, are translated from the same mRNA.
1991,
Pubmed
Ferry,
Globin gene silencing in primary erythroid cultures. An inhibitory role for interleukin-6.
1997,
Pubmed
Flodby,
Expression of the liver-enriched transcription factors C/EBP alpha, C/EBP beta, HNF-1, and HNF-4 in preneoplastic nodules and hepatocellular carcinoma in rat liver.
1995,
Pubmed
Foka,
Molecular characterization of the Xenopus CCAAT-enhancer binding protein beta gene promoter.
2001,
Pubmed
,
Xenbase
Graham,
A new technique for the assay of infectivity of human adenovirus 5 DNA.
1973,
Pubmed
Heinrich,
Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway.
1998,
Pubmed
Hibi,
Signal transduction through cytokine receptors.
1998,
Pubmed
Hirano,
Interleukin 6 and its receptor: ten years later.
1998,
Pubmed
Hughes,
A novel role of Sp1 and Sp3 in the interferon-gamma -mediated suppression of macrophage lipoprotein lipase gene transcription.
2002,
Pubmed
Isshiki,
Reciprocal expression of NF-IL6 and C/EBP in hepatocytes: possible involvement of NF-IL6 in acute phase protein gene expression.
1991,
Pubmed
Jones,
The soluble interleukin 6 receptor: mechanisms of production and implications in disease.
2001,
Pubmed
Kockar,
Analysis of the Xenopus laevis CCAAT-enhancer binding protein alpha gene promoter demonstrates species-specific differences in the mechanisms for both auto-activation and regulation by Sp1.
2001,
Pubmed
,
Xenbase
Legraverend,
High level activity of the mouse CCAAT/enhancer binding protein (C/EBP alpha) gene promoter involves autoregulation and several ubiquitous transcription factors.
1993,
Pubmed
Li,
c-Myc represses transcription in vivo by a novel mechanism dependent on the initiator element and Myc box II.
1994,
Pubmed
Liao,
Transcriptional inhibition by interleukin-6 of the class A macrophage scavenger receptor in macrophages derived from human peripheral monocytes and the THP-1 monocytic cell line.
1999,
Pubmed
Mead,
Interferon-gamma stimulates the expression of the inducible cAMP early repressor in macrophages through the activation of casein kinase 2. A potentially novel pathway for interferon-gamma-mediated inhibition of gene transcription.
2003,
Pubmed
Menéndez-Hurtado,
Characterization of the promoter region of the rat CCAAT/enhancer-binding protein alpha gene and regulation by thyroid hormone in rat immortalized brown adipocytes.
2000,
Pubmed
Nakajima,
Phosphorylation at threonine-235 by a ras-dependent mitogen-activated protein kinase cascade is essential for transcription factor NF-IL6.
1993,
Pubmed
Nakajima,
Identification of a novel interleukin-6 response element containing an Ets-binding site and a CRE-like site in the junB promoter.
1993,
Pubmed
Poli,
The role of C/EBP isoforms in the control of inflammatory and native immunity functions.
1998,
Pubmed
Poli,
IL-6DBP, a nuclear protein involved in interleukin-6 signal transduction, defines a new family of leucine zipper proteins related to C/EBP.
1990,
Pubmed
Ramji,
The two C/EBP isoforms, IL-6DBP/NF-IL6 and C/EBP delta/NF-IL6 beta, are induced by IL-6 to promote acute phase gene transcription via different mechanisms.
1993,
Pubmed
Ramji,
CCAAT/enhancer-binding proteins: structure, function and regulation.
2002,
Pubmed
Rana,
The DNA binding activity of C/EBP transcription factor is regulated in the G1 phase of the hepatocyte cell cycle.
1995,
Pubmed
Sabatakos,
Expression of the genes encoding CCAAT-enhancer binding protein isoforms in the mouse mammary gland during lactation and involution.
1998,
Pubmed
Sengupta,
Inhibition of cytokines and JAK-STAT activation by distinct signaling pathways.
1996,
Pubmed
Tang,
Role of C/EBP homologous protein (CHOP-10) in the programmed activation of CCAAT/enhancer-binding protein-beta during adipogenesis.
2000,
Pubmed
Terstegen,
Differential inhibition of IL-6-type cytokine-induced STAT activation by PMA.
2000,
Pubmed
Timchenko,
Autoregulation of the human C/EBP alpha gene by stimulation of upstream stimulatory factor binding.
1995,
Pubmed
Trautwein,
Transactivation by NF-IL6/LAP is enhanced by phosphorylation of its activation domain.
1993,
Pubmed
Wegner,
Calcium-regulated phosphorylation within the leucine zipper of C/EBP beta.
1992,
Pubmed
Welm,
Translational induction of liver-enriched transcriptional inhibitory protein during acute phase response leads to repression of CCAAT/enhancer binding protein alpha mRNA.
2000,
Pubmed
Xing,
IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses.
1998,
Pubmed
Xu,
Expression profiling suggested a regulatory role of liver-enriched transcription factors in human hepatocellular carcinoma.
2001,
Pubmed
Zador,
Renal CCAAT/enhancer-binding proteins in experimental diabetes mellitus.
1998,
Pubmed