Title of project : Mechanisms underlying angiotensin II-stimulated production of proinflammatory cytokines : Are transcription factors involved?
| Project/Area Number |
15590209
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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 | National University Corporation 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) |
MIYOSHI Michio Tottori University, Faculty of Medicine, Research Associate, 医学部, 助手 (20093627)
NAGATA Katumi Tottori University, Graduate School of Medical Science, Research Associate, 医学系研究科, 助手 (30208011)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2003: ¥500,000 (Direct Cost: ¥500,000)
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| Keywords | angiotensin II / AT_1 receptor / NF-κB / AP-1 / LPS / IL-1 / rat |
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| Research Abstract |
We recently reported an involvement of angiotensin II(ANG II) and ANG type 1(AT1) receptor in the hepatic, splenic and brain expression of IL-1ss induced in rats by lipopolysaccharide(LPS). We investigated whether ANG II contributes to the IL-1 production through its effect on the activation of proinflammatory transcription factors, NF-κB and AP-1, induced in the rat's liver and spleen by LPS. Surprisingly, LPS induced a marked increase in the hepatic activation of NF-κB, an effect that was significantly enhanced (rather than reduced) by pre-treatment with the ACE inhibitor and AT1-receptor antagonist. Furthermore, the LPS-induced expression of splenic AP-1 was significantly augmented by pre-treatment with the AT1-receptor antagonist. The present results suggest that endogenous ANG II or AT1 receptor suppress the activation of the hepatic or splenic transcription factors in LPS-treated rats. Our results does not seem to support the idea that NF-κB and AP-1 play a key role in the ANG II-enhanced production of proinflammatory cytokines induced by LPS in rats.
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Report
(3 results)
Research Products
(10 results)
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[Publications] Miyoshi, M., Nagata, K., Imoto, T., Goto, O., Ishida, A., Watanabe, T.: "ANG II is involved in the LPS-induced production of proinflammatory cytokines in dehydrated rats"American Journal of Physiology. 284. R1092-R1097 (2003)
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[Publications] Shimizu, H., Miyoshi, M., Matsumoto, K., Goto, O., Imoto, T, Watanabe, T.: "The effects of central injection of angiotensin-converting enzyme inhibitor and the angiotensin type1 receptor antagonist on the induction by lipopolysaccharide of fever and brain interleukin-1β response in rats"The Jpurnal of Pharmacology and Experimental Therapeutics. 308. 865-873 (2004)
