| Project/Area Number |
07557016
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (A)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 試験 |
|---|
| Research Field |
Pathological medical chemistry
|
|---|
| Research Institution | University of Tokyo |
|---|
Principal Investigator |
SHIMIZU Takao University of Tokyo, Faculty of Medicine, Department of Biochemistry, Professor, 医学部, 教授 (80127092)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Motonao Japan Tobacco Company, Life Science Research Institute, Research Fellow, 生命科学研究所, 研究員
KUME Kazuhiko University of Tokyo, Faculty of Medicine, Department of Biochemistry, Assistant, 医学部, 助手 (30251218)
IZUMI Takashi University of Tokyo, Faculty of Medicine, Department of Biochemistry, Assistant, 医学部, 助手 (70232361)
|
|---|
| Project Period (FY) |
1995 – 1996
|
| Project Status |
Completed (Fiscal Year 1996)
|
| Budget Amount *help |
¥13,200,000 (Direct Cost: ¥13,200,000)
Fiscal Year 1996: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1995: ¥8,200,000 (Direct Cost: ¥8,200,000)
|
|---|
| Keywords | endotoxin / platelet activating factor / PAF / tyrosine phosphorylation / MAP kinase |
|---|
| Research Abstract |
Endotoxin causes systemic collapse, disseminated intravascular coagulation and lethality, by infection of gram-negative bacteria. Although many reports the production of cytokines, the precise mechanism of pathophysiological events remained obscure. By cell biology and molecular biology techniques, we obtained following results.
(1) Elucidation of relation between endotoxin and PAF receptor
We established transgenic mice overxpressing PAF receptor. These mice showed severe symptoms of endotoxin shock and death by intravenous administration of small doses of LPS.The lethality was efficiently blocked by the use of PAF receptor antagonists, suggesting that PAF-PAFR is involved in the pathogenesis of endotoxin-induced lethality.
(2) Elucidation of LPS action on macrophages
By incubating of macrophages with bacterial endotoxin, PAFR mRNA was increased several fold after 4h. MAP kinase was also activated, and the activation related to the tyrosine phosphorylation of Raf-1 kinase.
|
