| Project/Area Number |
14570243
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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 |
Bacteriology (including Mycology)
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| Research Institution | KITASATO UNIVERSITY |
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Principal Investigator |
KUMAZAWA Yoshio KITASATO UNIV., SCHOOL OF SCIENCE, PROFESSOR, 理学部, 教授 (30072375)
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| Co-Investigator(Kenkyū-buntansha) |
TAKIMOTO Hiroaki KITASATO UNIV., SCHOOL OF SCIENCE, LECTURER, 理学部, 講師 (00253534)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | TOLL-LIKE RFCEPTOR / BACTERIAL GLYCOLIPID / MACROPHAGE / LIPID RAFT / NF-κB / NF-κB / 結核菌糖脂質 / Toll-like receptor |
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| Research Abstract |
Analysis of TLRs recognized bacterial glycolipid
Trehalose 6,6-dimycolate (TDM), present in the envelope of mycobacteria, exerts a number of immunomodifying effects. The mechanisms by which TDM activates macrophages via Toll-like receptors (TLRs) have not been clear yet. When peritoneal macrophages were stimulated with mycobacterial TDM, TNF-α levels were significantly higher in culture supernatants of macrophages from TLR4-deficient C57BL/10ScCr (B10Cr) than the wild-type C57BL/10ScSn (B10Sn) mice. In cultures of macrophages from TLR2 knockout mice, TDM-induced TNF-α production significantly reduced compared with that from B10Sn mice. Mycobacterial TDM exhibited stronger TNF-α-inducing activity than rhodococcal TDM. Glycolipids separated from Rhodococcus sp. consist of mycolic acid with shorter carbon chain of alkyl group than mycobacterial one. The activation of NF-κB in HEK293 cells over-expressed mouse TLR2 by both TDM was very weak. Among compounds tested, the strongest activation of NF-κB was detected in TLR2-transfectani stimulated with rhodococcal TMM. Taken together, macrophage activation by TDM and mycolic acid-containing glycolipids seems to occur via the interaction of TLR2 and another receptor such as TLR6.
Role of lipid raft formation in TLR2 signaling
Mycobacterial lipoarabinomannan (LAM) was recognized by TLR2, and stimulation with LAM caused accumulation of TLR2 to the lipid rafts on the membrane of macrophages. Depletion of cholesterol from membrane of macrophages failed to produce any cytokines after stimulation with LAM.
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