NF-kappaB regulates intestinal epithelial cell and bile salt-induced migration after injury.
OBJECTIVE
To determine if NF-kappa B regulates intestinal epithelial cell migration and if it has a role during bile salt-induced migration.


BACKGROUND
Mucosal restitution is an important repair modality in the gastrointestinal tract. The authors have shown that taurodeoxycholate (TDCA) increases intestinal epithelial cell migration. NF-kappa B regulates activation of a number of genes involved in inflammatory responses.


METHODS
Studies were conducted in IEC-6 cells. I kappa B protein expression was determined by Western blot analysis. Sequence-specific NF-kappa B binding activity was measured by EMSA shift assays and nuclear localization by immunohistochemistry. Cell migration was examined by using an in vitro model that mimics the early cell division-independent stages of epithelial restitution.


RESULTS
The process of cell migration over the wounded area was associated with a significant increase in NF-kappa B binding activity in IEC-6 cells. Immunohistochemistry revealed translocation of NF-kappa B into the nucleus. Western blot analysis showed that injury decreased I kappa B protein expression. Inhibition of the binding activity by treatment with a specific NF-kappa B inhibitor, MG-132, inhibited cell migration during restitution. Further, exposure to TDCA at the physiologic concentration that induces intestinal epithelial cell migration increased NF-kappa B binding activity, induced NF-kappa B translocation into the nucleus, and decreased I kappa B protein expression. MG-132 also inhibits bile salt-induced cell migration.


CONCLUSIONS
NF-kappa B regulates intestinal epithelial cell migration. Bile salts at physiologic concentrations increase cell migration by activation of NF-kappa B. These data show that bile salts may have a role in the maintenance of intestinal mucosal integrity.
Strauch
Eric D
ED
Department of Surgery, University of Maryland School of Medicine, 22 South Greene Street, Baltimore, MD 21201, USA. estrauch@umaryland.edu
Bass
Barbara L
BL
Rao
Jaladanki N
JN
Vann
Jennifer A
JA
Wang
Jian-Ying
JY
D000818:Animals; D001647:Bile Acids and Salts; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D007413:Intestinal Mucosa / Q000166:cytology* / Q000187:drug effects / Q000293:injuries; D007976:Leupeptins / Q000494:pharmacology; D016328:NF-kappa B / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D013657:Taurodeoxycholic Acid / Q000494:pharmacology
D001647:Bile Acids and Salts; D007976:Leupeptins; D016328:NF-kappa B; D013657:Taurodeoxycholic Acid; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde