Angiotensin II inside and outside the brain: investigation on the mechanism of angiotensin II-induced
| Project/Area Number |
17590593
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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 |
General internal medicine (including Psychosomatic medicine)
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| Research Institution | Tottori University |
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Principal Investigator |
MIYOSHI Michio Tottori University, Faculty of Medicine, Research Associate, 医学部, 助手 (20093627)
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| Co-Investigator(Kenkyū-buntansha) |
IMOTO Toshiaki Tottori University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (10109639)
WATANABE Tathuo Tottori University, Faculty of Medicine, Professor, 医学部, 教授 (60182929)
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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 |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2006: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2005: ¥500,000 (Direct Cost: ¥500,000)
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| Keywords | ANG II / LPS / cytokines / microglial cell / NF-κB / AP-1 / NO / morphological change / 視床下部 / 海馬 / 発熱 |
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| Research Abstract |
We investigated whether proinflammatory transcription factors [nuclear factor-κB (NF-κB) and activator protein-1 (AP-1)] contribute to the angiotensin II (ANG II)-dependent production of cytokines within the brain. Interestingly, we found that a single i.c.v. injection of lipopolysaccharide (LPS) had no effect on NF-κB and AP-1 activities in the hypothalamus, hippocampus, and cerebellum (except for a decrease in hypothalamic AP-1 activity). Furthermore, both an angiotensin-converting-enzyme (ACE) inhibitor and an ANG type 1 (AT_1) receptor antagonist enhanced (rather than reduced) the NF-κB and AP-1 activities in the hippocampus and/or cerebellum of rats given LPS. These results seem not to support the idea that NF-κB and AP-1 play key roles in the ANG II-induced enhancement of the production of proinflammatory cytokines that is induced by LPS in the rat's brain. However, only a portion of whole brain cells is occupied by brain macrophage, microglial cells. Therefore, we then investiga
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ted whether ANG II and its receptors contributes to LPS-induced microglial activations through their effect on the activation of NF-κB and AP-1. To this end, examined were the effects of an ATI receptor antagonist, losartan, on the LPS-induced productions of interleukin-1 (IL-1) and nitric oxide (NO), morphological changes of the cells, as well as the activations of NF-κB and AP-1 in primary culture of microglial cells. Our RT-PCR study revealed that LPS-stimulated microglial cells had marked expression of mRNAs for ATI receptor. LPS-stimulated microglial cells showed increases in IL-1 and nitrite concentrations, as well as a morphological change. These effects were all inhibited by treatment with losartan. The activity of NF-κB and AP-1 was enhanced in LPS-stimulated microglial cells, that were significantly suppressed by losartan. Application of ANG II itself enhanced the LPS-induced increase in nitrite concentration. Collectively, these results suggest that the production of pyrogenic cytokines may be enhanced by ANG II and AT_1 receptor that stimulate microglial cells through the activation of transcription factors, NF-κB and AP-1 Less
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Report
(3 results)
Research Products
(13 results)
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[Journal Article] Effects of central injection of angiot ensin-converting-enzyme inhibitor and angiotensin type 1 receptor antagonist on the brain NF-κB and AP-1 activities of rats given LPS2006
Author(s)
Watanabe, K, Taniguchi, M., Miyoshi, M., Shimizu, H., Imoto, T, Sato, K, Watanabe, T.
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Journal Title
Peptides 27(6)
Pages: 1538-1546
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Systemic administration of polymyxin B induces hypothermia in rats via an inhibitory effect on metabolic rate.2006
Author(s)
Moriyama, N., Miyoshi, M., Imoto, T., Maruyama, M., Shido, O., Watanabe, T.
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Journal Title
European Journal of Pharmacology 541(1-2)
Pages: 38-43
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Are transcription factors NF-κB and AP-1 involved in the ANG II-stimulated production of proinflammatory cytokines induced by LPS in dehydrated rats?2005
Author(s)
Sasaki, K., Taniguchi, M., Miyoshi, M., Goto, O., Sato, K., Watanabe, T.
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Journal Title
American Journal of Physiology 289(6)
Description
「研究成果報告書概要(欧文)」より
Related Report
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