ArticleNucleic acids research2003
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.
Article in Nucleic acids research, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 20 citations in OpenAlex.
- Chronic and Transient Hyperglycemia Induces Changes in the Expression Patterns ofInternational journal of molecular sciences · 2021Article
- Interleukin-6 induces impairment in human subcutaneous adipogenesis in obesity-associated insulin resistance.Diabetologia · 2016Article
- Chronic inflammation contributes to the development of hepatocellular carcinoma by decreasing miR-122 levels.Oncotarget · 2016Article
- Human monocytes accelerate proliferation and blunt differentiation of preadipocytes in association with suppression of C/EBPΑ mRNA.Obesity (Silver Spring, Md.) · 2012Article
- The expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 in human macrophages is inhibited by the anti-atherogenic cytokine transforming growth factor-β and requires Smads, p38 mitogen-activated protein kinase and c-Jun.The international journal of biochemistry & cell biology · 2011Article
- Induction of multilineage markers in human myeloma cells and their down-regulation by interleukin 6.International journal of hematology · 2007Article
- A critical role for the Sp1-binding sites in the transforming growth factor-beta-mediated inhibition of lipoprotein lipase gene expression in macrophages.Nucleic acids research · 2005Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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