| Project/Area Number |
21590077
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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 |
Biological pharmacy
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| Research Institution | Toho University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
NAGATA Kisaburo 東邦大学, 理学部, 准教授 (10291155)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 免疫学 / 一酸化窒素 / 黄色ブドウ状球菌 / 好中球 / アポトーシス / 炎症 / 黄色ブドウ球菌 / マクロファージ / ケモカイン / iNOS / サイトカイン |
|---|
| Research Abstract |
During inflammation, neutrophils infiltrate into the involved site and undergo apoptosis. Early apoptotic neutrophils are then cleared by phagocytes, leading to resolution of the inflammation, whereas if late apoptotic neutrophils are accumulated for some reason, they provoke pro-inflammatory responses such as TNF-α production. In order to determine how endogenously produced nitric oxide(NO) regulates neutrophil apoptosis and the resolution of inflammation, we compared peritoneal inflammation induced by Staphylococcus aureus bioparticles in wild type mice with that in inducible NO synthase(iNOS)-deficient ones. In this model, NO production was largely dependent on iNOS, the NO level peaking at 24h. There were increases in the numbers of neutrophils and late apoptotic ones at 24h in iNOS-deficient mice as compared with in wild type ones, and consequently TNF-α production at 36h in iNOS-deficient mice. On the other hand, the administration of a NO donor to iNOS-deficient mice at 12h decreased the numbers of neutrophils and late apoptotic ones at 24h, and thereafter TNF-α production at 36h. In addition, coculturing of macrophages with late apoptotic neutrophils caused TNF-α production and a NO donor inhibited the transmigration of neutrophils in a dose-dependent manner. Collectively, these results suggest a novel mechanism that endogenously produced NO suppresses neutrophil accumulation at a late stage of inflammation, thereby preventing the appearance of late apoptotic neutrophils and subsequent pro-inflammatory responses.
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