Study on the function of receptor for Helicobacter pylori VacA and the mechanism of its intoxication
| Project/Area Number |
17209015
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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, Tropical Medicine, Professor, 熱帯医学研究所, 教授 (50050696)
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| Co-Investigator(Kenkyū-buntansha) |
WADA Akihiro Nagasaki University, Institute of Tropical Medicine, Lecturer, 熱帯医学研究所, 講師 (70253698)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥50,050,000 (Direct Cost: ¥38,500,000、Indirect Cost: ¥11,550,000)
Fiscal Year 2006: ¥26,390,000 (Direct Cost: ¥20,300,000、Indirect Cost: ¥6,090,000)
Fiscal Year 2005: ¥23,660,000 (Direct Cost: ¥18,200,000、Indirect Cost: ¥5,460,000)
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| Keywords | Helicobacter pylori / VacA / AZ-521 cells / COX-2 / PGE_2 / p38 MAP kinase / ATF-2 cascade / Bacterial toxin / Pathogenesis |
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| Research Abstract |
By 2006 budget, we found that VacA increases PGE_2 production by AZ-521 cells by up-regulation of COX-2 expression through a signaling pathway involving the p38 MAP kinase/ATF-2 cascade, leading to activation of the CRE element on the COX-2 promoter.
Treatment of AZ-521 cells with Helicobacter pylori VacA increased cyclooxygenase-2 (COX-2) mRNA in a time-and dose-dependent manner. A p38 MAP kinase (MAPK) inhibitor, SB203580, blocked elevation of COX-2 mRNA levels, whereas PD98059, which blocks the Erkl/2 cascade, partially suppressed the increase. Consistent with involvement of p38 MAPK, VacA-induced accumulation of COX-2 mRNA was reduced in AZ-521 cells overexpressing a dominant-negative p38 MAPK (DN-p38). Phosphatidylinositol-specific phospholipase C, which inhibits VacA-induced p38 MAPK activation, blocked VacA-induced COX-2 expression. In parallel with COX-2 expression, VacA increased PGE_2 production, which was inhibited by SB203580 and NS-398, a COX-2 inhibitor. VacA-induced PGE2 production was markedly attenuated in AZ-521 cells stably expressing DN-p38. VacA increased transcription of a COX-2 promoter reporter gene and activated a COX-2 promoter containing mutated NF-kB or NF-IL6 sites, but not a mutated CRE site, suggesting direct involvement of the ATF-2/CREB-binding region in VacA-induced COX-2 promoter activation. The reduction of ATF-2 expression in AZ-521 cells transformed with ATF-2-siRNA resulted in suppression of COX-2 expression. Thus, we found that VacA enhances PGE_2 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.
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Report
(3 results)
Research Products
(15 results)
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[Journal Article] Helicobacter pylori vacuolating cytotoxin induces activation of the proapoptotic protein Bax, leading to cytochrome c release and cell death, independent of vacuolation2006
Author(s)
Yamasaki E., Wada A., Kumatori A., Nakagawa I., Funao J., Nakayama M., Hisatsune J., Kimura M., Moss J., Hirayama T.
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Journal Title
J. Biol. Chem. 281
Pages: 11250-11259
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Endoscope disinfection using chlorine dioxide in an automated washer-disinfector.2006
Author(s)
Isomoto H., Urata M, Kawazoe K, Matsuda J, Nishi Y, Wada A, Ohnita K, Hirakata Y, Matsuo N, Inoue K, Hirayama T, Kamihira S, Kohno S.
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Journal Title
J. Hosp. Infect 63
Pages: 298-305
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Helicobacter pylori VacA clustering in lipid rafts, mediated by receptor, RPTP β, is required for intoxication in AZ-521 cells.2006
Author(s)
Nakayama M, Hisatsune J, Yamasaki E, Nishi Y, Wada A, Kurazono H, Sap J, Yahiro K, Moss J, Hirayama T
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Journal Title
Infect Immun 74
Pages: 6571-6580
Description
「研究成果報告書概要(欧文)」より
Related Report
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