| Project/Area Number |
13557022
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | Nagasaki University |
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Principal Investigator |
HITAYAMA Toshiya Nagasaki University, Institute of Tropical Medicine, Professor, 熱帯医学研究所, 教授 (50050696)
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| Co-Investigator(Kenkyū-buntansha) |
MAKINO Souichi Obihiro University of Agriculture and Veterinary Medicine, Research Center for Animal Hygiene and Food Safety, Professor, 畜産学部, 教授 (30181621)
AOYAMA Nobuo Kobe University School of Medicine, Kobe University Hospital, Associate Professor, 医学部付属病院, 助教授 (30243299)
WADA Akihiro Nagasaki University, Institute of Tropical Medicine, Lecturer, 熱帯医学研究所, 講師 (70253698)
YAHIRO Kinnosuke Chiba University, Graduate School of Medicine, Research Associate, 大学院・医学研究院, 助手 (80345024)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥13,800,000 (Direct Cost: ¥13,800,000)
Fiscal Year 2003: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥6,600,000 (Direct Cost: ¥6,600,000)
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| Keywords | Helicobacier pylori / vacuolating cytotoxin / VacA toxin / toxicity / bacterial toxin / vaccine / ヘリコバクター・ピロリ / 成分ワクチン / VacA / CagPAI / ワクチン開発 / 病原遺伝子群 |
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| Research Abstract |
Persistent infection with Helicobacter pylori causes chronic active gastritis, which predisposes the mucosa to peptic ulceration, and is believed to participate in the pathogenesis of gastric carcinoma and primary gastric lymphoma (i.e., mucosa-associated lymphoid tissue, or MALT type). Although H. pylori is a noninvasive bacterium that survives in the stomach mucosa, pathogenic strains of H. pylori produce and secrete a potent vacuolating cytotoxin, VacA.
Oral administration of VacA to mice caused acute inflammation of the gastric mucosa with accumulation of mast cells, the activation of which by VacA resulted in production of proinflammatory cytokines. Our previous studies showed that RPTPβ serves as a receptor for VacA On AZ-521 cells, a human gastric cancer cell line.
In. this study, oral administration of VacA to wild-type mice, but not to RPTPb KO mice, resulted in gastric ulcers, suggesting that RPTPβ is essential for intoxication by VacA in gastric tissue
Thus, our animal experiments have demonstrated that VacA is a major virulence factor associated with the damage to gastric mucosa through binding to RPTPβ. This finding also supports that VacA may be good vaccine candidate for prevention from H. pylori-induced gastritis and ulceration.
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