Strauch Eric D, Bass Barbara L, Rao Jaladanki N, Vann Jennifer A, Wang Jian-Ying
Department of Surgery, University of Maryland School of Medicine, 22 South Greene Street, Baltimore, MD 21201, USA.
Ann Surg. 2003 Apr;237(4):494-501. doi: 10.1097/01.SLA.0000060459.03270.E7.
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.
确定核因子-κB（NF-κB）是否调节肠上皮细胞迁移以及它在胆盐诱导的迁移过程中是否发挥作用。
黏膜修复是胃肠道重要的修复方式。作者已表明牛磺脱氧胆酸盐（TDCA）可增加肠上皮细胞迁移。NF-κB调节许多参与炎症反应的基因的激活。
在IEC-6细胞中进行研究。通过蛋白质免疫印迹分析测定IκB蛋白表达。通过电泳迁移率变动分析（EMSA）测定序列特异性NF-κB结合活性，并通过免疫组织化学测定核定位。使用模拟上皮修复早期不依赖细胞分裂阶段的体外模型检测细胞迁移。
IEC-6细胞中，伤口区域上的细胞迁移过程与NF-κB结合活性显著增加相关。免疫组织化学显示NF-κB易位至细胞核。蛋白质免疫印迹分析表明损伤降低了IκB蛋白表达。用特异性NF-κB抑制剂MG-132处理抑制结合活性，可抑制修复过程中的细胞迁移。此外，在诱导肠上皮细胞迁移的生理浓度下暴露于TDCA可增加NF-κB结合活性，诱导NF-κB易位至细胞核，并降低IκB蛋白表达。MG-132也抑制胆盐诱导的细胞迁移。
NF-κB调节肠上皮细胞迁移。生理浓度的胆盐通过激活NF-κB增加细胞迁移。这些数据表明胆盐可能在维持肠黏膜完整性中发挥作用。
