| Project/Area Number |
15590087
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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 |
Biological pharmacy
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| Research Institution | Yamagata Promotional Organization for Industrial Technology (2004)
Yamagata Public Corporation For the Development Of Industry, Institute Life Support Technology (2003) |
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Principal Investigator |
YOSHIMURA Tetsuhiko Yamagata Promotional Organization for Industrial Technology, Institute for Life Support Technology, Deputy Director General, 生物ラジカル研究所, 副所長 (70271517)
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| Co-Investigator(Kenkyū-buntansha) |
KASAI Shigenobu Yamagata Promotional Organization for Industrial Technology, Institute for Life Support Technology, Deputy Director General, 生物ラジカル研究所, 研究員 (70342730)
MORITA Hidetoshi Azabu University, School of Veterinary Medicine, Associate Professor, 獣医学部, 助教授 (70257294)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Helicobacter pylori / endotoxin / nitric oxide / gastric mucosa / inducible nitric oxide synthase / cyclooxygenase / inflammatory cytokine / 誘導型NO合成酵素(iNOS) / シクロオキシゲナーゼ(COX) |
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| Research Abstract |
Helicobacter pylori, a gram-negative bacterium, is the primary cause of gastritis and a major contributor to peptic ulcer disease. Despite its importance as a human pathogen, principal factor of pathogenicity of the bacterium remains to be identified Nitric oxide (NO) released due to the induction of Ca^<2+> independent isoform of nitric oxide synthase (iNOS) by lipopolysaocharide or endotoxin from a gram-negative bacterium bas been known to be deleterious to a gastric mucosa. In the present shady, to elucidate the physiological action of H.pylori LPS on gastric mucosa and the role of NO, we were carried out both in vivo and in vitro study by employing E.coli LPS as a control.
1. IT pylori LPS was isolated from gram-order bacteria by the phenol-water extraction method, and then further purified by tine enzymatic digestion of RNA, DNA, and proteins.
2. In vitro cross talk between products from iNOS and cyclooxygenase (COX) in the rat gastric mucosa during endotoxemia was examined in vivo. The results demonstrate that in the E cob LPS-treated rat gastric mucosa, PGE2, a COX product, enhances after activation of iNOS. The effect of COX activity on iNOS-NO pathway is important in the regulation of gastric mucosal integrity inflammatory states.
3. We further elucidated the interaction of LPS with gastric epithelial cells by using a normal mouse gastric surface mucous cell line (GSM06). Our findings suggest that both LPSs from H.pylori and E.coli induce the iNOS and Toll-like receptor (TLR) 2 through the TLR 4 expressed constitutively in GSM06. This mechanism on TLR 2 induction can be crucial for maintenance of gastric mucosal integrity.
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