| Project/Area Number |
11670137
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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 |
Pathological medical chemistry
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| Research Institution | Gunma University (2000)
The University of Tokyo (1999) |
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Principal Investigator |
IZUMI Takashi Gunma University, School of Medicine, Professor, 医学部, 教授 (70232361)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Takao University of Tokyo, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (80127092)
OBINATA Hideru ]Gunma University, School of Medicine, Associate, 医学部, 助手
谷口 雅彦 東京大学, 大学院・医学系研究科, 助手 (70260346)
横溝 岳彦 東京大学, 大学院・医学系研究科, 助手 (60302840)
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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 |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | LIPID MEDIATORS / RECEPTORS / LEUKOTRIENES / PAF / ACUTE LUNG INFLAMMATION / ACUTE RENAL INFLAMMATION / HEPATECTOMY / 炎症性疾患 / 遺伝子改変マウス |
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| Research Abstract |
Lipid mediators such as leukotrienes (LTs) and platelet-activating factor (PAF) are major chemical mediators involved in inflammatory and allergic disorders. To clarify the pathological roles of these mediators in inflammatory disorders, this research project was carried out, and following results were obtained.
1. Establishment and analysis of inflammatory animal model
In PAF receptor transgenic mice, PAF receptor deficiency mice, cPLA2 deficiency mice, and wild-type mice, ARDS (adult respiratory distress syndrome) models were made by intratracheal administration of acid or intravenous administration of LPS, and analyzed. The obtained results indicate that PAP and cPLA2-dependent mediators play important roles in these conditions.
PAF receptors are overexpressed in Kupffer cells after experimental hepatectomy in rat.
2. Study on LTB4 receptor
The mechanism of leukocyte-specific expression of LTB4 receptor was revealed by its promoter analysis. Using in vivo chemotaxis of CHO cells expressing LTB4 receptor, the possible roles of LTB4 in pathogenesis of acute renal inflammation were indicated. The second receptor for LTB4 was discovered. The project on establishment of LTB4 deficiency mice is now in progress.
3. Signal transduction through LTD4 receptor
Intracellular signal transduction through LTD4 receptor was analyzed in monocytes and macrophages.
4. Intracellular localization of enzymes involved in production of lipid mediators
The mechanisms of intracellular localization and translocation of enzymes such as cPLA2, 5-lipoxygenase and LTA4 hydrolase were studied.
These results revealed that mechanisms of lipid mediator production and pathological roles of lipid mediators in inflammatory disorders, and may help us develop new therapies and drugs.
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