Regulation of cyclooxygenase 2 expression in hepatocytes by CCAAT/enhancer-binding proteins

Nuria A. Callejas, Lisardo Boscá, Christopher S. Williams, Raymond N. DuBois, Paloma Martin-Sanz

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Abstract

Background and Aims: Expression of cyclooxygenase (COX)-2 in response to lipopolysaccharide (LPS) challenge has been analyzed in cultured fetal, neonatal, and adult hepatocytes and in hepatoma cell lines. Methods: To study the mechanisms of LPS-dependent expression of COX-2 in these cells, the activity of the COX-2 promoter and the levels of CCAAT/enhancer-binding proteins (C/EBPs) were determined. Results: COX-2 was induced in fetal hepatocytes, but this response declined rapidly after birth. This loss of inducibility of COX-2 paralleled the expression of C/EBP-α in neonatal hepatocytes. Transfection of fetal and adult hepatocytes with sequences corresponding to the 5'-flanking region of the rat COX-2 gene confirmed the absence of promoter activity in adult hepatocytes. Moreover, transient expression of C/EBP-α, but not C/EBP-δ, in the hepatoma cell line AT3F cells abolished the COX-2 promoter activity. Prolonged culture of adult hepatocytes restored the induction of COX-2 after complete disappearance of C/EBP-α. Conclusions: These results suggest that the presence of high levels of C/EBP-α is involved in the impairment of COX-2 expression in adult hepatocytes challenged with proinflammatory stimuli.

Original languageEnglish (US)
Article number49468
Pages (from-to)493-501
Number of pages9
JournalGastroenterology
Volume119
Issue number2
DOIs
StatePublished - Jan 1 2000

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ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Callejas, N. A., Boscá, L., Williams, C. S., DuBois, R. N., & Martin-Sanz, P. (2000). Regulation of cyclooxygenase 2 expression in hepatocytes by CCAAT/enhancer-binding proteins. Gastroenterology, 119(2), 493-501. [49468]. https://doi.org/10.1053/gast.2000.9374