Mechanisms of prostaglandin E2 production, secretion, and exclusion in the brain during fever.
| Project/Area Number |
16390059
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Osaka Institute of Technology (2005-2006)
Kyoto University (2004) |
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Principal Investigator |
MATSUMURA Kiyoshi Osaka Institute of Technology, Faculty of Information Science and Technology, Professor, 情報科学部, 教授 (10157349)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Shigeo Kyoto University, Graduate School of Informatics, Professor, 情報学研究科, 教授 (40124797)
HOSOKAWA Hiroshi Kyoto University, Graduate School of Informatics, Lecturer, 情報学研究科, 講師 (90359779)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 2006: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2004: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Keywords | prostaglandin / cyclooxygenase / fever / phospholipase A2 / arachidonic acid / brain endothelial cell / organic anion transporter / arachnoidal membrane / 脳 / ボスホリパーゼA2 / 内皮細胞 / サイトカイン / nuclear factor kappa B / iPLA2 / 抗炎症作用 / cycloxygenase-2 |
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| Research Abstract |
Mechanism of prostaglandin E_2 (PGE_2) production during fever
・Microsomal prostaglandin E synthase (mPGES) is indispensable for brain PGE_2 production induced by lipopolysachharide (LPS).
・In mice, LPS induces cyclooxygenase-2 (COX-2) in brain endothelial cells but not mPGES MPGES is constitutively expressed in arachnoidal membrane. These results suggest that trans-cellular biosynthesis of PGE_2 takes place in endothelial cells and arachnoidal cells.
・Calcium-independent PLA_2 (iPLA_2) is involved in LPS-induced fever
・iPLA_2 also suppresses LPS-induced COX-2 in the brain, and LPS-induced inflammatory cytokines, suggesting its multiple roles in inflammatory reaction to LPS.
・Arachidonic acid (AA), the major product of PLA_2, induces COX-2 in brain endothelial cells, when injected into the brain. This result means that AA is not only the substrate for PGE_2 biosynthesis but also an inducer of COX-2.
・AA-induced COX-2 induction is due to the direct action of AA rather than indirect action via AA metabolites.
・Interleukin-6 plays an essential role in carrageenan-induced COX-2 expression in brain endothelial cells.
Brain expression of organic anion transporters which possibly transport PGE_2
・Prostaglandin transporter (PGT) is constitutively expressed in arachnoidal membrane of the rat brain
・LPS induces further PGT transcription in arachnoidal membrane and brain endothelial cells.
・Multidrug resistance protein 4 (MRP4) is expressed in brain endothelial cells.
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] Cellular and molecular bases of the initiation of fever2006
Author(s)
Steiner AA, Ivanov AI, Serrats J, Hosokawa H, Phayre AN, Robbins JR, Roberts JL, Kobayashi S, Matsumura K, Sawchenko PE, Romanovsky AA
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Journal Title
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] Cellular and molecular bases of the initiation of fever.2006
Author(s)
Steiner AA, Ivanov AI, Serrats J, Hosokawa H, Phayre AN, Robbins JR, Roberts JL, Kobayashi S, Matsumura K, Sawchenko PE, Romanovsky AA.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Cellular and molecular bases of the initiation of fever2006
Author(s)
Steiner AA, Ivanov AI, Serrats J, Hosokawa H, Phayre AN, Robbins JR, Roberts JL, Kobayashi S, Matsumura K, Sawchenko PE, Romanovsky AA
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Related Report
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[Journal Article] Direct pyrogenic input from prostaglandin EP3 receptor-expressing preoptic neurons to the dorsomedial hypothalamus2005
Author(s)
Nakamura, Y., Nakamura, K., Matsumura, K., Kobayashi, S., Kaneko, T., Morrison, SF.
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Journal Title
Eur.J.Neurosci. 22
Pages: 3137-3146
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[Journal Article] TRPM8 protein localization in trigeminal ganglion and taste papillae2005
Author(s)
Abe, J., Hosokawa, H., Okazawa, M., Kandachi, M., Sawada, Y., Yamanaka, K., Matsumura, K., Kobayashi, S.
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Journal Title
Brain Res Mol Brain Res 136
Pages: 91-98
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