| Project/Area Number |
09671848
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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 |
Morphological basic dentistry
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| Research Institution | Asahi University (1998)
Osaka University (1997) |
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Principal Investigator |
OGAWA Tomohiko Asahi University, School of Dentistry, Department of Oral Microbiology, Professor, 歯学部, 教授 (80160761)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | lipid A / LPS / Helicobacter pylori / Porphyromonas gingivalis / compound 506 / Endotoxic property / Immunobiological activity / Cytokine |
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| Research Abstract |
Helicobacter pylori lipid A exhibited no or very low endotoxic activities i.e., lethal toxicity in galactosamine-loaded mice, pyrogenicity for rabbits and the activity of the Limulus test when compared with Escherichia coli-type synthetic lipid A (compound 506). The endotoxic properties of H.pylon lipid A were also a little weaker than those of the low endotoxic lipid A of P.gingivalis. The mitogenic activity of H.pylori lipid A in murine splenic mononuclear cells was also less than those of P.gingivalis lipid A and compound 506. On the other hand, H.pylori lipid A induced comparable production of interleukin-6 (IIL-6) by human peripheral blood mononuclear cells (PBMC) as compared with P.gingivalis lipid A and compound 506. H.pylori lipid A also increased definitely human natural killer cell activity, and strongly agglutinated rabbit erythrocytes. However, the lipid As of H.pylori and P.gingivalis showed lower activities in inducing tumor necrosis factor alpha (TNF-alpha) production by human PBMC and IL-8 production by human gingival fibroblasts than that of compound 506. The structural feature of H.pylori lipid A may be associated with low endotoxic properties and potent immunobiological activities. Futher, a systemic infection by Gram-negative bacteria results in septic shock which is mainly caused by macrophages stimulated with endotoxic lipopolysaccharides (LPS). The administration of non-toxic lipid A of P.gingivalis results in lower induction of IL-1beta production and its mRNA expression, whereas the lipid A exhibited higher calmodulin kinase activation in comparison with that of endotoxic synthetic lipid A of E.coli in alveolar macrophages of galactosamine-loaded mice. A calmodulin kinase activator and anti-IL-beta monoclonal antibody also protected mice against endotoxic lipid A-induced lethal toxicity.
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