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


METHODS
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.


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-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.


CONCLUSIONS
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.
Strauch
Eric D
ED
Department of Surgery, University of Maryland, Baltimore, MD 21201, USA.
Yamaguchi
Jon
J
Bass
Barbara L
BL
Wang
Jian-Ying
JY
D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D003840:Deoxycholic Acid / Q000502:physiology*; D005786:Gene Expression Regulation / Q000235:genetics; D007413:Intestinal Mucosa / Q000473:pathology / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology*; D051381:Rats; D013656:Taurocholic Acid / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics*
D016328:NF-kappa B; D016212:Transforming Growth Factor beta; D003840:Deoxycholic Acid; D013656:Taurocholic Acid