CCAAT/enhancer binding proteins beta and delta regulate alpha1-acid glycoprotein gene expression in rat intestinal epithelial cells.
Isoforms of CCAAT/enhancer binding protein (C/EBP) are expressed in rodent intestine as well as in the rat intestinal epithelial cell line IEC-6. However, no specific roles have been attributed to these isoforms in intestinal epithelial cells. To determine whether C/EBP family members could be implicated in the regulation of acute-phase response gene expression in intestinal epithelial cells, we have studied the effect of glucocorticoids on expression of the alpha1-acid glycoprotein gene and C/EBP isoforms in IEC-6 cells. Glucocorticoids induced alpha1-acid glycoprotein gene expression in these cells. This induction coincided with an increase of DNA-binding capacity of both C/EBPbeta and C/EBPdelta to the B1 and B2 C/EBP-interacting sites localized in the rat AGP promoter. Transforming growth factor beta, (TGFbeta), a cytokine involved in the transcriptional regulation of several acute-phase plasma proteins, antagonized the glucocorticoid-dependent induction of alpha1-acid glycoprotein gene expression. In parallel, TGFbeta downregulated the DNA-binding capacities of both the C/EBPbeta and C/EBPdelta isoforms. Mutations of the B1 or the B2 C/EBP-interacting site strongly reduced the responsiveness of the alpha1-acid glycoprotein promoter to glucocorticoids and TGFbeta. These results demonstrate a functional role for C/EBPbeta and C/EBPdelta in rat intestinal epithelial cells and suggest that these isoforms represent important modulators of the acute-phase response and of glucocorticoid, as well as TGFbeta, responsiveness.
Boudreau
F
F
Département d'Anatomie et de Biologie Cellulaire, Faculté de Médecine, Université de Sherbrooke, Québec, Canada.
Yu
S J
SJ
Asselin
C
C
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004347:Drug Interactions; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D009961:Orosomucoid / Q000096:biosynthesis* / Q000235:genetics; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D005938:Glucocorticoids; D009687:Nuclear Proteins; D009961:Orosomucoid; D016212:Transforming Growth Factor beta; D003907:Dexamethasone