Bile salts regulate intestinal epithelial cell migration by nuclear factor-κB-induced expression of transforming growth factor-β

BACKGROUND: Mucosal restitution is an important repair modality in the gastrointestinal tract. We have shown that taurodeoxycholate increases intestinal epithelial cell migration by increasing TGF-β expression, and that the transcription factor NF-κB 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-κB regulates TGF-β expression. STUDY DESIGN: Studies were conducted in IEC-6 cells. Cell migration was examined using an in vitro model. TGF-β protein and mRNA expression was determined by ELISA and Northern blot analysis. Sequence-specific NF-κB binding activity was measured by gel shift assays. RESULTS: 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-κB binding activity. Inhibition of NF-κB activity significantly inhibited cell migration during restitution and resulted in a significant decrease in TGF-β mRNA expression and protein expression. CONCLUSIONS: We conclude that bile salts at physiologic conditions increase cell migration after injury, an effect regulated by NF-κB. Further, NF-κB elicits TGF-β gene transcription during cell migration. These data support a physiologic role of bile salts in the maintenance of intestinal mucosal integrity.