| Project/Area Number |
11670278
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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 |
Bacteriology (including Mycology)
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| Research Institution | Aichi Medical University School of Medicine |
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Principal Investigator |
YOKOCHI Takashi Aichi Medical University School of Medicine, Department of Microbiology and Immunology, Professor, 医学部, 教授 (20126915)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | endotoxin / nitric oxide / LPS / vascular endothelial cell / TNF / interferon-gamma / inducible type NO synthase / END-D cell / 血管内皮細胞 / CD14 / 組織因子 / TF / HUVEC / DIC |
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| Research Abstract |
Effect of interferon-gamma(IFN-γ), tumor-necrosis factor-alpha(TNF-α)and lipopolysaccharide(LPS)on nitric oxide(NO)production in mouse vascular aortic endothelial cell line END-D was examined. LPS, TNF-α, and a lower concentration of IFN-γ inhibited NO production in END-D cells, while a higher concentration of IFN-γ definitely enhanced it. The NO production induced by a high concentration of IFN-γ was further augmented in combination with LPS or TNF-α. In the sequential incubation of LPS and IFN-γ, the enhancement of NO production required the prior treatment with IFN-γ. Stimulation of END-D cells with a high concentration of IFN-γ led to the expression of inducible type NO synthase(iNOS). The augmentation of NO production by IFN-γ alone or in combination with LPS or TNF-α was completely blocked by several inhibitors of iNOS.It was strongly suggested that a higher concentration of IFN-γ itself enhanced NO production in END-D cells through the expression of iNOS.LPS and TNF-α exclusively modulated the activity of iNOS which expression was once tiggered by IFN-γ. On the other hand, a lower concentration of IFN-γ.LPS and TNF-α reduced NO production through down-regulating constitutive type NOS.It was suggested that proinflammatory cytokines may be involved in LPS-induced vascular endothelial injury via NO production.
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