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

N. A. Callejas, L. Bosca, C. S. Williams, R. N. DuBois, P. Martin-Sanz

Research output: Contribution to journalArticle

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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)
Pages (from-to)493-501
Number of pages9
JournalGastroenterology
Volume119
Issue number2
StatePublished - 2000
Externally publishedYes

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CCAAT-Enhancer-Binding Proteins
Cyclooxygenase 2
Hepatocytes
Lipopolysaccharides
Hepatocellular Carcinoma
Cell Line
5' Flanking Region
Transfection
Parturition

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Callejas, N. A., Bosca, 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.

Regulation of cyclooxygenase 2 expression in hepatocytes by CCAAT/enhancer-binding proteins. / Callejas, N. A.; Bosca, L.; Williams, C. S.; DuBois, R. N.; Martin-Sanz, P.

In: Gastroenterology, Vol. 119, No. 2, 2000, p. 493-501.

Research output: Contribution to journalArticle

Callejas, NA, Bosca, L, Williams, CS, DuBois, RN & Martin-Sanz, P 2000, 'Regulation of cyclooxygenase 2 expression in hepatocytes by CCAAT/enhancer-binding proteins', Gastroenterology, vol. 119, no. 2, pp. 493-501.
Callejas NA, Bosca L, Williams CS, DuBois RN, Martin-Sanz P. Regulation of cyclooxygenase 2 expression in hepatocytes by CCAAT/enhancer-binding proteins. Gastroenterology. 2000;119(2):493-501.
Callejas, N. A. ; Bosca, L. ; Williams, C. S. ; DuBois, R. N. ; Martin-Sanz, P. / Regulation of cyclooxygenase 2 expression in hepatocytes by CCAAT/enhancer-binding proteins. In: Gastroenterology. 2000 ; Vol. 119, No. 2. pp. 493-501.
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