| Project/Area Number |
17590204
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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 |
Environmental physiology (including Physical medicine and Nutritional physiology)
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| Research Institution | Tottori University |
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Principal Investigator |
WATANABE Tatsuo Tottori University, Faculty of Medicine, Professor, 医学部, 教授 (60182929)
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| Co-Investigator(Kenkyū-buntansha) |
IMOTO Toshiaki Tottori University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (10109639)
MIYOSHI Michio Tottori University, Faculty of Medicine, Research Associate, 医学部, 助手 (20093627)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | ANP / LPS / IL-1 / fever / rat / NF-κB / AP-1 / microglial cell / NO / 形態変化 / 脾臓 / 脳 / アンギオテンシンII |
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| Research Abstract |
We investigated whether natriuretic peptide (NP) acts as an endogenous antipyretic inside and/or outside the blood-brain barrier in rats made febrile by intravenous (i.v.) injection of bacterial endotoxin (lipopolysaccharide ; LPS). LPS induced a triphasic fever, the second phase of which was significantly enhanced by an i.v. injection of the NP-receptor antagonist HS-142-1. In contrast., the same antagonist (i.v.) had no effect on the fever induced by i.v. injection of interleukin-β (IL-1β). An i.v. administration of HS-142-1 enhanced the LPS (i.v.)-induced IL-1β response in the rat spleen. An i.v. treatment with atrial NP (ANP) significantly attenuated the second phase of the LPS-induced fever. Intracerebroventricular (i.c.v.) injection of the above NP-receptor antagonist resulted in an augmentation of the third phase of the fever induced by i.v. administration of LPS, the same phase that, was attenuated by ANP given i.c.v. When given i.c.v., the antagonist had no effect on the fever
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induced by i.v. IL-1β. On the other hand, we used primary cultures of rat brain macrophage-like cells (i.e., microglial cells) to investigate whether ANP binding to its receptors inhibits LPS-induced microglial activation via effects on the activation of the proinflammatory transcription factors NF-κB and AP-1. UPS-stimulated microglial cells showed increases in nitrite and IL-1 concentrations, and in the expression of IL-1 mRNA, as well as a morphological change from an amoeboid shape to a multipolar rod shape. These effects were all significantly inhibited by treatment with ANP. The inhibition by ANP of the LPS-induced nitrite response was abrogated by HS-142-1. NF-κB and AP-1 activities were enhanced in LPS-stimulated microglial cells, and these enhancements were significantly suppressed by ANP. Collectively, these results suggest that the production of pyrogenic cytokines may be inhibited by NP acting inside and outside the blood-brain barrier, leading to an inhibition of the fever in rats. Less
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