Regulation of expression of human intestinal bile acid-binding protein in Caco-2 cells

Abstract

Molecular mechanisms of the bile acid active transport system in the ileal enterocytes remain unknown. We examined whether bile acids affect human enterocyte gene expression of intestinal bile acid-binding protein (I-BABP), a component of this transport system. Differentiated Caco-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 medium 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 treated bile showed any difference in I-BABP mRNA expression from the control. Bile acid treatment increased the level of I-BABP mRNA in Caco-2 cells in a time- and dose-dependent manner. Western blot analysis showed that this induction led to increase in cytosolic I-BABP. Chenodeoxycholic acid and deoxycholic acid showed greater induction effects than other hydrophilic bile acids, including their own glycine conjugates. Pretreatment by actinomycin D or cycloheximide completely inhibited the up-regulation of I-BABP expression by bile acid. Bile acids, especially lipophilic bile acids, increase the I-BABP expression in Caco-2-cells, suggesting that luminal bile acids play an important role in regulating the I-BABP gene expression.