Role of NF-kappaB in the growth, differentiation and apoptosis of gastric epithelial cells

我们已经表明，幽门螺旋杆菌感染的扩大型折叠胃炎的特征是巨噬细胞和多核细胞的明显浸润，白细胞介素-1 β的高分泌和高胃泌素血症。本研究旨在探讨胃泌素对胃上皮细胞nf - κ b活化的影响。为此，我们将胃泌素受体cDNA导入MKN28胃癌细胞，建立了稳定表达胃泌素受体的细胞系。利用该细胞系和分离的豚鼠胃上皮细胞，我们获得了以下结果：1. 胃泌素激活NF-kappaB，而NF-kappaB被蛋白激酶C （PKC）抑制剂抑制。2. 引入显性负IKK、NIK或TRAF6抑制胃泌素诱导的NF-kappa活化。3. 无论是乙洛特勒素抑制pkc - δ还是显性阴性pkc - δ抑制胃泌素诱导的NF-kappa 4的激活。胃泌素在5分钟内激活胃上皮细胞的pkc - δ，这种作用持续超过60分钟。5. 将pkc - δ cDNA单独导入胃上皮细胞能够激活NF-kappaB，同时转染显性阴性IKK、NIK或TRAF6可以抑制这种作用。本研究的数据表明，胃蛋白酶通过激活nf - κ b促进胃炎症。

We have shown that enlarged fold gastritis with H. pylori infection is characterized by marked infiltrates of macrophages and polynuclear cells, high production of interleukin-1 beta and hypergastrinemia. The present study was performed to investigate the effects of gastrin on activation of NF-kappaB in gastric epithelial cells. For this purpose, we created a cell line stably expressing gastrin receptor by introducing gastrin receptor cDNA into MKN28 gastric cancer cells. Using this cell line and isolated guinea-pig gastric epithelial cells, we obtained the following results. 1. Gastrin activates NF-kappaB, which was inhibited by protein kinase C (PKC) inhibitors. 2. Introduction of dominant negative IKK, NIK, or TRAF6 inhibited gastrin-induced activation of NF-kappa. 3. Inhibition of PKC-delta by eitherrottlerin or dominant negative PKC-delta inhibited gastrin-induced activation of NF-kappa 4.Gastrin activates PKC-delta in gastric epithelial cells within 5 minutes and this effect persisted for over 60 minutes. 5. Introduction of PKC-delta cDNA into gastric epithelial cells alone was able to activate NF-kappaB and this effect was inhibited by cotransfection of dominant negative IKK, NIK, or TRAF6. The data presented here suggest that gastsin promotes gastric inflammation through activation of NF-kappaB.