CCAAT ENHANCER-BINDING PROTEIN-BETA AND PROTEIN-DELTA REGULATE ALPHA(1)-ACID GLYCOPROTEIN GENE-EXPRESSION IN RAT INTESTINAL EPITHELIAL-CELLS

Isoforms of CCAAT/enhancer binding protein (C/EBP) are expressed in ro dent intestine as well as in the rat intestinal epithelial cell line I EC-6, However, no specific roles have been attributed to these isoform s in intestinal epithelial cells, To determine whether C/EBP family me mbers could be implicated in the regulation of acute-phase response ge ne expression in intestinal epithelial cells, we have studied the effe ct of glucocorticoids on expression of the alpha(1)-acid glycoprotein gene and C/EBP isoforms in IEC-6 cells. Glucocorticoids induced alpha( 1)-acid glycoprotein gene expression in these cells. This induction co incided with an increase of DNA-binding capacity of both C/EBP beta an d C/EBP delta to the B1 and B2 C/EBP-interacting sites localized in th e rat AGP promoter. Transforming growth factor beta, (TGF beta), a cyt okine involved in the transcriptional regulation of several acute-phas e plasma proteins, antagonized the glucocorticoid-dependent induction of alpha(1)-acid glycoprotein gene expression. In parallel, TGF beta d ownregulated the DNA-binding capacities of both the C/EBP beta and C/E BP delta isoforms, Mutations of the B1 or the B2 C/EBP-interacting sit e strongly reduced the responsiveness of the alpha 1-acid glycoprotein promoter to glucocorticoids and TGF beta, These results demonstrate a functional role for C/EBP beta and C/EBP beta in rat intestinal epith elial cells and suggest that these isoforms represent important modula tors of the acute-phase response and of glucocorticoid, as well as TGF beta, responsiveness.