Bile salts regulate intestinal epithelial cell migration by nuclear factor-kappa B-induced expression of transforming growth factor-beta.

Abstract

Mucosal restitution is an important repair modality in the gastrointestinal tract. We have shown that taurodeoxycholate increases intestinal epithelial cell migration by increasing TGF-beta expression, and that the transcription factor NF-kappa B regulates TDCA induced cell migration after injury. The objectives of this study were to determine if this is a property shared by other bile salts or an effect specific to TDCA, and to determine if NF-kappa B regulates TGF-beta expression. Studies were conducted in IEC-6 cells. Cell migration was examined using an in vitro model. TGF-beta protein and mRNA expression was determined by ELISA and Northern blot analysis. Sequence-specific NF-kappa B binding activity was measured by gel shift assays. Taurocholate and deoxycholate at physiologic concentrations significantly increased intestinal epithelial cell migration 6 hours after wounding (p < 0.01), and was associated with a significant increase in specific NF-kappa B binding activity. Inhibition of NF-kappa B activity significantly inhibited cell migration during restitution and resulted in a significant decrease in TGF-beta mRNA expression and protein expression. We conclude that bile salts at physiologic conditions increase cell migration after injury, an effect regulated by NF-kappa B. Further, NF-kappa B elicits TGF-beta gene transcription during cell migration. These data support a physiologic role of bile salts in the maintenance of intestinal mucosal integrity.