2001 Fiscal Year Final Research Report Summary
Identification and validation of novel virulence factors of Helicobacter pylori
| Project/Area Number |
12670459
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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 | THE UNIVERSITY OF TOKYO |
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Principal Investigator |
YOSHIDA Haruhiko HOSPITAL, The University of Tokyo, ASSISTANT, 医学部・附属病院, 助手 (60240305)
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| Co-Investigator(Kenkyū-buntansha) |
OGURA Keiji HOSPITAL, The University of Tokyo, FELLOW, 医学部・附属病院, 医員
SHIRATORI Yasushi HOSPITAL, The University of Tokyo, LECTURER, 医学部・附属病院, 講師 (70196624)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Helicobacter pylori / CagA / cagPAI / Mongolian gerbil / intracellular signaling pathways / virulence |
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| Research Abstract |
First, we sought to confirm previously reported virulence factors, especially cagPAI. We compared anti-CagA antibody seropositivity between gastric cancer patients and matched controls by using recombinant CagA (a product of cagPAI) and found that anti-CagA positivity was associated with an odds ratio of 10 concerning gastric cancer. We also validated virulence of cagPAI in Mongolian gerbils using cagPAI gene knocked out mutants, showing that inflammation and tumorogenesis require cagPAI.
Next, we investigated H. pylori-mediated induction of intracellular signaling pathways and demonstrated activation of NF-kappa B through IKK and TRAFs ; of SRE and AP-1 through the ERK cascade ; and of cyclin D1 through the MAPK cascade. The presence of cagPAI and direct contact between bacteria and host cells were required in the induction of those intracellular signals. We applied cDNA microarray analysis to examine various gene expressions in the host cells.
Finally, we established a short-term Mongolian gerbil infection model to validate H. pylori virulence factors in vivo.
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Research Products
(26 results)
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[Publications] Maeda S, Yoshida H, Ogura K, Yamaji Y, Ikenoue T, Mitsushima T, Tagawa H, Kawaguchi R, Mori K, Mafune K, Kawabe T, Shiratori Y, Omata M: "Assessment of gastric carcinoma risk associated with Helicobacter pylori may vary depending on the antigen used -CagA specific enzyme-linked immunoadsorbent assay (ELISA) versus commercially available H. pylori ELISAs"Cancer. 88. 1530-1535 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Maeda S, Yoshida H, Ogura K, Mitsuno Y, Hirata Y, Yamaji Y, Akanuma M, Shiratori Y, Omata M: "H. pylori activates NF-kappa B through a signaling pathway involving I kappa B kinases, NF-kappa B- inducing kinase, TRAF2, and TRAF6 in gastric cancer cells"Gastroenterology. 119. 97-108 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Akanuma M, Maeda S, Ogura K, Mitsuno Y, Hirata Y, Ikenoue T, Otsuka M, Watanabe T, Yamaji Y, Yoshida H, Kawabe T, Shiratori Y, Omata M: "The uvalutionof putative virulence factors of Helicobacter pylori for gastroduodenal disease using short-term Mongolian gerbil infection model"Journal of Infectious Disease. 185. 341-347 (2002)
Description
「研究成果報告書概要(欧文)」より
