2002 Fiscal Year Final Research Report Summary
Role of NF-kappaB in the growth, differentiation and apoptosis of gastric epithelial cells
| Project/Area Number |
13670515
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Osaka University |
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Principal Investigator |
MIYAZAKI Yoshiji Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30303960)
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| Co-Investigator(Kenkyū-buntansha) |
KIYOHARA Tatsuya Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (50322178)
SHINOMURA Yasuhisa Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (90162619)
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| Project Period (FY) |
2001 – 2002
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| Keywords | NF-kappaB / H-pylori / gastrin / gastric epithelial cells / IKK / protein kinase C / NIK / TRAF6 |
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| Research Abstract |
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.
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