| Project/Area Number |
08670611
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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 | Osaka City University |
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Principal Investigator |
ARAKAWA Tetsuo Osaka City University, Medical School, Associate Professor, 医学部, 助教授 (60145779)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIWARA Yasuhiro Osaka City University, Medical School, Research Associate, 医学部, 助手 (40285292)
HIGUCHI Kazuhide Osaka City University, Medical School, Lecture, 医学部, 講師 (20218697)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | Helicobacter pylori / cytotoxin / gastric mucosa / inflammatory cytokine / interleukin-1beta / cell proliferation / epidermal growth factor / neutrophil / Halicobacter pylori / Helicobacter pylori / サイトカイン / 胃潰瘍 |
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| Research Abstract |
Helicobacter pylori infection in the gastric mucosa is strongly associated with chronic type B gastritis and peptic ulcer disease. However the pathogenic mechanisms of the H.pylori related disease is not known. Cytotoxin, which is produced by H.pylori and induces vacuolization in the target cells, is one of the major causative factors. In this research project, we focused on the role of the H.pylori cytotoxin in the gastric mucosa and examined whether H.pylori cytotoxin affects proliferation of the gastric cells and inflammatory cytokine production such as interleukin-1 beta (IL-1beta) and tumor necrosis factor- alpha (TNF- alpha) by human monocytes. We found that 1) H.pylori cytotoxin inhibited growth and proliferation of phuman gastric cultured cells and interferes with epidermal growth factor (EGF) binding to its receptor on the cell surface. 2) H.pylori stimulated inflammatory cytokine production and expression of messenger RNA by human isolated monocytes. 3) Prostaglandin E_2, which plays a central role in the gastric mucosal defense, inhibited H.pylori-induced inflammatory production by human monocytes. 4) These inflammatory cytokine induced gastric ulcer recurrence through increased expression of adhesion molecules and neutrophil infiltration in the rat experimental models and induced MCP-1 expression at the ulcer margin. 5) Interleukin-8 which is high concentration in the H.pylori infected gastric mucosa stimulated intraepithelial margination of neutrophils and impaired epithelial barrier function in the in vitro models. 6) Immunohistochemical study using human biopsy specimens of the H.pylori infected mucosa showed increased expression of ICAM-1, LFA-1, and Mac-1 in the gastric mucosa. These findings contributes pathogenesis of H.pylori related disease and the role of H.pylori cytotoxin in the gastric mucosa.
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