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

    Research output: Contribution to journalArticlepeer-review

    51 Scopus citations

    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 - 2000

    ASJC Scopus subject areas

    • Hepatology
    • Gastroenterology

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