The inflammation-induced down-regulation of plasma Fetuin-A (α2HS-glycoprotein) in liver results from the loss of interaction between long C/EBP isoforms at two neighbouring binding sites

Christophe Gangneux, Maryvonne Daveau, Martine Hiron, Céline Derambure, John Papaconstantinou, Jean Philippe Salier

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Fetuin-A is an hepatic protein whose mRNA transiently falls during the inflammatory acute phase via unknown transcriptional mechanisms. Various FETUA promoter/cat constructs transiently transfected in the Hep3B hepatoma cell line allowed us to identify four NF-1 and C/EBP binding sites (N, C) arranged in a 5′-N2-C2-N1-C1-3′ order and required for basal promoter activity. Mutant constructs demonstrated that C1 and C2 but not N1 nor N2 are required for the cytokine-driven down-regulation of the promoter. A variable spacing between C2 and N1 showed that the alignment of the (C1+N1) and (C2+N2) areas is critical for the promoter activity in quiescent but not cytokine-stimulated cells. Co-transfection of a plasmid only producing either a long or short C/EBPβ isoform prevented FETUA regulation by cytokines. Electromobility shift assays with liver nuclear extracts showed that during the acute phase the complexes formed over N1 and N2 are not modified whereas short C/EBPα and -β isoforms replace the long isoforms bound to C1 and C2 in the quiescent liver. Therefore the basal promoter activity requires an interaction between the long C/EBP isoforms bound to C1 and C2 whereas the inflammation-induced down-regulation results from the loss of interaction between the cytokine-induced, short C/EBP isoforms.

Original languageEnglish (US)
Pages (from-to)5957-5970
Number of pages14
JournalNucleic Acids Research
Volume31
Issue number20
DOIs
StatePublished - Oct 15 2003

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alpha-2-HS-Glycoprotein
Glycoproteins
Protein Isoforms
Down-Regulation
Binding Sites
Inflammation
Liver
Cytokines
Liver Extracts
Transfection
Hepatocellular Carcinoma
Cats
Plasmids
Cell Line
Messenger RNA
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

The inflammation-induced down-regulation of plasma Fetuin-A (α2HS-glycoprotein) in liver results from the loss of interaction between long C/EBP isoforms at two neighbouring binding sites. / Gangneux, Christophe; Daveau, Maryvonne; Hiron, Martine; Derambure, Céline; Papaconstantinou, John; Salier, Jean Philippe.

In: Nucleic Acids Research, Vol. 31, No. 20, 15.10.2003, p. 5957-5970.

Research output: Contribution to journalArticle

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