| 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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