| 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)
北村 信次 大阪大学, 医学部・附属病院, 医員
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
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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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