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

NF-κB在胃上皮细胞生长、分化和凋亡中的作用

• 批准号: 13670515
• 负责人: MIYAZAKI Yoshiji
• 金额: $ 2.3万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670515/
• 关键词: NF-kappaB; H-pylori; gastrin; gastric epithelial cells; IKK; protein kinase C; NIK; TRAF6

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.

我们已经证明，H。幽门螺杆菌感染的特征在于巨噬细胞和多核细胞的显著浸润、白细胞介素-1 β的高产生和高胃泌素血症。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，我们通过将胃泌素受体cDNA导入MKN 28胃癌细胞中，建立了稳定表达胃泌素受体的细胞系。使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-κ B，而NF-κ B被蛋白激酶C（PKC）抑制剂抑制。2.引入显性阴性IKK、NIK或TRAF 6抑制胃泌素诱导的NF-κ活化。3.抑制PKC-δ或显性失活PKC-δ均能抑制胃泌素诱导的NF-κ 4活化。胃泌素在5分钟内激活胃上皮细胞PKC-δ，这种作用持续60分钟以上。5.将PKC-δ cDNA单独导入胃上皮细胞能够激活NF-κ B，并且这种效应被显性阴性IKK、NIK或TRAF 6共转染抑制。本文提供的数据表明，胃泌素通过激活NF-κ B促进胃炎症。

项目成果

M.Toyama, et al.: "Peroxisome proliferator-activated receptor γ reduces the growth rate of pancreatic cencer cells though the reduction of cyclin D1"Life Sci. (in press).

M. Toyama 等人：“过氧化物酶体增殖物激活受体 γ 通过减少细胞周期蛋白 D1 降低胰腺癌细胞的生长速度”Life Sci（出版中）。

Y.Miyazaki, et al.: "Epidermal growth factor receptor mediates stress-induced expression of its ligands in rat gastric epithelial cells"Gastroenterology. 121(1). 108-116 (2001)

Y.Miyazaki 等人：“表皮生长因子受体介导大鼠胃上皮细胞中应激诱导的配体表达”胃肠病学。

M.Toyota, et al.: "Peroxisome proliferator-activated receptor γ reduces the growth rate of pancreatic cencer cells through the reduction of cvclin D1"Life Sci. 121(1). 1565-1575 (2002)

M.Toyota 等人：“过氧化物酶体增殖物激活受体 γ 通过减少 cvclin D1 降低胰腺癌细胞的生长速度”Life Sci 121(1) (2002)。

M.Toyota, et al.: "Gastrin activate NF-κB through a protein kinase C-dependent pathway involving NF-κB-inducting kinase, IκB kinase and TRAF6 in MKN-28 cells transfected with gastrin receptor"Gut. (in press).

M. Toyota 等人：“胃泌素通过蛋白激酶 C 依赖性途径激活 NF-κB，该途径涉及转染胃泌素受体的 MKN-28 细胞中的 NF-κB 诱导激酶、IκB 激酶和 TRAF6”（正在出版）。 。

M.Toyota, et al.: "Peroxisome proliferator-activated receptor γ reduces the growth rate of pancreatic cencer cells through the reduction of cyclin D1"Life Sci. 121(1). 1565-1575 (2002)

M.Toyota 等人：“过氧化物酶体增殖物激活受体 γ 通过减少细胞周期蛋白 D1 降低胰腺癌细胞的生长速度”Life Sci. 121(1) (2002)。