NF-κB Regulates Intestinal Epithelial Cell and Bile Salt-Induced Migration After Injury

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