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

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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.