Objective: To determine if NF-κB regulates intestinal epithelial cell migration and if it has a role during bile salt-induced migration. Summary Background Data: Mucosal restitution is an important repair modality in the gastrointestinal tract. The authors have shown that taurodeoxycholate (TDCA) increases intestinal epithelial cell migration. NF-κB regulates activation of a number of genes involved in inflammatory responses. Methods: Studies were conducted in IEC-6 cells. IκB protein expression was determined by Western blot analysis. Sequence-specific NF-κB 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-κB binding activity in IEC-6 cells. Immunohistochemistry revealed translocation of NF-κB into the nucleus. Western blot analysis showed that injury decreased IκB protein expression, inhibition of the binding activity by treatment with a specific NF-κB inhibitor, MG-132, inhibited cell migration during restitution. Further, exposure to TDCA at the physiologic concentration that induces intestinal epithelial cell migration increased NF-κB binding activity, induced NF-κB translocation into the nucleus, and decreased IκB protein expression. MG-132 also inhibits bile salt-induced cell migration. Conclusions: NF-κB regulates intestinal epithelial cell migration. Bile salts at physiologic concentrations increase cell migration by activation of NF-κB. These data show that oile salts may have a role in the maintenance of intestinal mucosal integrity.
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