| Project/Area Number |
19209014
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | Nagasaki University |
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Principal Investigator |
HIRAYAMA Toshiya Nagasaki University, 熱帯医学研究所, 教授 (50050696)
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| Co-Investigator(Kenkyū-buntansha) |
ISOMOTO Hajime 長崎大学, 大学病院, 講師 (90322304)
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| Project Period (FY) |
2007 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥49,920,000 (Direct Cost: ¥38,400,000、Indirect Cost: ¥11,520,000)
Fiscal Year 2009: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Fiscal Year 2008: ¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2007: ¥24,180,000 (Direct Cost: ¥18,600,000、Indirect Cost: ¥5,580,000)
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| Keywords | ヘリコバクター・ピロリ / VacA / 細菌毒素 / 毒性発現 / CagA / エフェクター / 毒素侵入 / エンドサイトーシス / P38 MAP kinase / ATF-2経路 / PI3K / Akt経路 / GSK3β / ATF-2 経路 / COX-2 / IL-8 |
|---|
| Research Abstract |
1) VacA may induce apoptosis by downregulation of anti-apoptotic Bcl-2 subfamily proteins via STAT3 inhibition. 2) VacA enhances PGE2 production by AZ-521 cells through induction of COX-2 expression via the p38 MAPK/ATF-2 cascade, leading to activation of the CRE site in the COX-2 promoter. 3) In promonocytic U937 cells, VacA directly increases IL-8 production by activation of the p38 MAPK via intracellular Ca^<2+> release, leading to activation of the transcription factors, ATF-2, CREB, and NF-kB. 4) VacA stimulated protein kinase B (Akt) activity via activation of PI3K, resulting in increased phosphorylation of its substrate, GSK3, with subsequent release of ■-catenin from a GSK3/■-catenin complex and its translocation to the nucleus, leading to activation of the cyclin D1 promoter. 5) Translocated CagA from H. pylori into gastric epithelial cells inhibit uptake and cytotoxicity of VacA via endocytosis inhibition in the cells. However, transfection of cagA gene did not affect the activation of p38 MAPK caused by VacA.
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