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

Callejas NA, Boscá L, Williams CS, DuBOIS RN, Martín-Sanz P
Gastroenterology. 2000 119 (2): 493-501

PMID: 10930384 · DOI:10.1053/gast.2000.9374

BACKGROUND & 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-alpha 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-alpha, but not C/EBP-delta, 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-alpha.

CONCLUSIONS - These results suggest that the presence of high levels of C/EBP-alpha is involved in the impairment of COX-2 expression in adult hepatocytes challenged with proinflammatory stimuli.

MeSH Terms (23)

Age Factors Animals Blotting, Western Carcinoma, Hepatocellular CCAAT-Enhancer-Binding Proteins Cyclooxygenase 2 DNA-Binding Proteins Female Fetus Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Isoenzymes Lipopolysaccharides Liver Microsomes Nuclear Proteins Pregnancy Prostaglandin-Endoperoxide Synthases Rats Rats, Wistar Transcriptional Activation Transfection Tumor Cells, Cultured

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