| Project/Area Number |
11557040
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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 |
Gastroenterology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
OMATA Masao Faculty of Medicin, The University of Tokyo, PROFESSOR, 医学部附属病院, 教授 (90125914)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Haruhiko Faculty of Medicin, The University of Tokyo, ASSISTANT, 医学部附属病院, 助手 (60240305)
NAKAO Masafumi Takeda Chemical Industries, SCIENTIST, 創薬研究本部, 首席研究員
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥12,800,000 (Direct Cost: ¥12,800,000)
Fiscal Year 2001: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1999: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Keywords | Helicobacter pylori / intracellular signaling pathways / cagPAI / Mongolian gerbil infection model / microarray / CagA / cagPAI / CagPAI / マイクロアレイ / 胃炎 / リン酸化 |
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| Research Abstract |
(1) NF-kB activation by H. pylori
We analyzed the molecular mechanism of H. pylori-mediated NF-kB activation in both a gastric epithelial cell line and in a monocytic cell line.
In gastric cancer cells, H. pylori possessing intact cag PAI activates NF-kB through a signaling pathway involving IkB kinases (IKK's), NF-kB-inducing kinase (NIK), TRAF2, and TRAF6. In a monocytic cell line, H. pylori-mediated NF-kB activation involves TLR4 but is independent of cag PAI.
(2) The activation of ERK/MARK cascade by H. pylori
H. pylori with intact cage PAI activated SRE, c-fos and Cyclin D1 transcription through the activation of ERK/MAPK cascade in human gastric cancer cells.
(3) SRE activation by CagA protein
It has been reported that CagA protein is translocated into epithelial cells and associated with cellular cytoskeletal rearrangements. We identified a new role of CagA protein as an activator of SRE.
(4) cDNA microarray analysis of H. pylori-mediated alteration of gene expression
We compared mRNA profiles in human gastric cancer cells with and without H. pylori cocultured by using an in-house cDNA microarray. Coculture with cag PAI positive strain significantly up-regulated mRNA expression in 8 of 2304 genes fested.
(5) Mongolian gerbil infection model
We examined the role of cag PAI in the gastric pathogenesis induced by H. pylori using a long-term (62 wk) animal model. Mongolian gerbils were challenged with TN2 and its isogenic mutants of cagE or vacA. No ulcer was found in the gerbils infected with the cagE mutant, and cagE mutants induced only mild gastritis cag PAI plays an essential role in the pathogenesis of gastric diseases related H. pylori infection.
Furthermore, we validated a 3-week gerbil model using isogenic mutants for screening of proinflammatory virulence determinants of H. pylori in vivo.
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