CCAAT/Enhancer Binding Proteins Beta and Delta Regulate α1-Acid Glycoprotein Gene Expression in Rat Intestinal Epithelial Cells

Publisher Website
Google Scholar
Abstract
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 α1-acid glycoprotein gene and C/EBP isoforms in IEC-6 cells. Glucocorticoids induced α1-acid glycoprotein gene expression in these cells. This induction coincided with an increase of DNA-binding capacity of both C/EBPβ and C/EBPδ to the B1 and B2 C/EBP-interacting sites localized in the rat AGP promoter. Transforming growth factor beta, (TGFβ), a cytokine involved in the transcriptional regulation of several acute-phase plasma proteins, antagonized the glucocorticoid-dependent induction of α1-acid glycoprotein gene expression. In parallel, TGFβ downregulated the DNA-binding capacities of both the C/EBPβ and C/EBPδ isoforms. Mutations of the B1 or the B2 C/EBP-interacting site strongly reduced the responsiveness of the α1-acid glycoprotein promoter to glucocorticoids and TGFβ. These results demonstrate a functional role for C/EBPβ and C/EBPδ in rat intestinal epithelial cells and suggest that these isoforms represent important modulators of the acute-phase response and of glucocorticoid, as well as TGFβ, responsiveness.