REGULATION OF EXPRESSION OF HUMAN INTESTINAL BILE ACID-BINDING PROTEIN IN CACO-2 CELLS

Molecular mechanisms of the bile acid active transport system in the i leal enterocytes remain unknown. We examined whether bile acids affect human enterocyte gene expression of intestinal bile acid-binding prot ein (I-BABP), a component of this transport system. Differentiated Cac o-2 cells were incubated in the presence of human bile, bile acids or other lipids, The level of I-BABP expression was evaluated by Northern and Western blot analyses. A 24 h incubation of Caco-2 cells in a med ium containing either bile or bile acids resulted in a remarkable 7.5- fold increase in the I-BABP mRNA level over the control level. Neither cholesterol, palmitic acid, phosphatidylcholine nor cholestyramine tr eated bile showed any difference in I-BABP mRNA expression from the co ntrol. Bile acid treatment increased the level of I-BABP mRNA in Caco- 2 cells in a time-and dose-dependent manner. Western blot analysis sho wed that this induction led to increase in cytosolic I-BABP. Chenodeox ycholic acid and deoxycholic acid showed greater induction effects tha n other hydrophilic bile acids, including their own glycine conjugates , Pretreatment by actinomycin D or cycloheximide completely inhibited the upregulation of I-BABP expression by bile acid, Bile acids, especi ally lipophilic bile acids, increase the I-BABP expression in Caco-2-c ells, suggesting that luminal bile acids play an important role in reg ulating the I-BABP gene expression.