| Project/Area Number |
10670359
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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 |
Public health/Health science
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| Research Institution | Nara Medical University |
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Principal Investigator |
KITA Eiji Nara Medical University, Bacteriology, Professor, 医学部・細菌学教室, 教授 (90133199)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUNO Fumiko Nara Medical University, Bacteriology, Assistant Researcher, 細菌学教室, 助手 (70271202)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | enterohemorrhagic E.coli / Shiga toxin / malnutrition / TNF-α / IL-10 / apoptosis / encephalopathy / vascular endothelial damage |
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| Research Abstract |
Shiga toxin (Stx)-producing Escherichia coli O157 : H7 infection in mice with protein-calorie-malnutrition leads to acute encephalopathy ; thereby, infected animals died within 10-12 days after infection. In infected mice, serum levels of TNF-α was increased 2 days after infection, 1 or 2 days after which Stx was detectable in the blood. Serum levels of IL-10 were also increased after day 5 of infection. In vitro studies, TNF-α accelerated the uptake of Stx by human umbilical venous endothelial cells (HUVEC) as well as the intracellular activation of Stx, which results in apoptosis in HUVEC. Such apoptosis induction was significantly enhanced by first exposing the cells to TNF-α for 6 h and subsequently by incubating them with Stx. IL-10 reduced the apoptosis induced by TNF-α and Stx. These results suggest that Stx damages vascular endothelial cells exposed to circulating TNF-α, thereby entering the brain through the damaged blood-brain barrier, and also that serum IL-10 may protect apoptosis in vascular endothelial cells.
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