1998 Fiscal Year Final Research Report Summary
Mechanism by which Helicobacter pylori infection causes gastric ulcers Mongolian gerbils
| Project/Area Number |
09470508
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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 | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Kyoto Pharmaceutical University |
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Principal Investigator |
OKABE Susumu Kyoto Pharmaceutical University, Department of Applied Pharmacology, Professor, 薬学部, 教授 (90012624)
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| Co-Investigator(Kenkyū-buntansha) |
AMAGASE Kikuko Kyoto Pharmaceutical University, Department of Applied Pharmacology, Research As, 薬学部, 助手 (60278447)
TAKAHASHI Satoru Kyoto Pharmaceutical University, Department of Applied Pharmacology, Associate P, 薬学部, 助教授 (20268098)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Helicobacter pylori / Mongolian gerbil / gastric ulcer / CINC / neutrophil / gastric acid / gastric mucuc / prostaglandin |
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| Research Abstract |
This study was designed to clarify the mechanism of Helicobocter pylori (H.pylori)-induced gastric ulcers in Mongolian gerbils. H.pylori of a VacA- and CagA-positive standard strain (NCTC11637) was once orally inoculated to the animals. H.pylori infection resulted in mucosal inflammation including neutrophil infiltration, associated with cytokine-induced neutrophil chemoattractant (CINC) expression. Thereafter, hemorrhagic lesions occurred in the fundus, followed by generation of ulcers in the same area. Eradication of H.pylori eliminated both CINC expression and gastritis with lesions. Inhibition of acid secretion by omeprazole also improved H.pylori-induced gastric pathology, On the other hand, H.pylori infection impaired mucus synthesis prior to ulceration, and exposure of gastric epithelial cells to H.pylori caused a marked decrease in mucus secretion. Interferon-gamma (IIFNgamma) was induced when gastritis became severe, and exerted a potent inhibitory effect on mucus secretion in the presence of H.pylori. Inhibition of prostaglandin (PG) synthesis by indomethcin accelerated H.pylori-induced gastric ulceration, although the drug did not cause any lesions or ulcers in normal animals. These results suggest that CINC, neutrophil infiltration, gastric acid and IFNgamma serve as deleterious factors in generation of H.pylori-induced gastric ulcers, while gastric mucus and PGs play protective roles in the gastric mucosa.
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