| Project/Area Number |
17390498
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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 |
Pathobiological dentistry/Dental radiology
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| Research Institution | Hokkaido University |
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Principal Investigator |
SHIBATA Ken-ichiro Hokkaido University, Graduate School of Dental Medicine, Professor., 大学院歯学研究科, 教授 (50145265)
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| Co-Investigator(Kenkyū-buntansha) |
KUROKI Yoshio Sapporo Medical University, School of Medicine, Professor, 医学部, 教授 (70161784)
YASUDA Motoaki Hokkaido University, Graduate School of Dental Medicine, associate Professor., 大学院歯学研究科, 助教授 (90239765)
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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 |
¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 2006: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2005: ¥9,200,000 (Direct Cost: ¥9,200,000)
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| Keywords | phagocytosis / Toll-like receptor / FSL-1 / DC-SIGN / Dectin-1 / CD14 / Th2 response / 微生物貪食 / リポペプチドFSL-1 / 大腸菌由来LPS / TLR2 |
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| Research Abstract |
Enormous lines of evidence have been accumulated that Toll-like receptors (TLRs) function as sensors for microbial invasion before uptake and degradation of bacteria. However, less is known about how signaling triggered by TLRs leads to phagocytosis of pathogens by phagocytes. This study was designed to determine whether stimulation of TLR2 with mainly the lipopeptide FSL-1 plays a role in phagocytosis of pathogens by macrophages. Diacylated lipopeptide FSL-1 markedly enhanced phagocytosis of S. aureus more strongly than that of E. coli; but did not enhance phagocytosis of latex beads. FSL-1 stimulation resulted in enhanced phagocytosis of bacteria by macrophages from TLR2+/+ mice but not those from TLR2-/-mice. Chinese hamster ovary cells stably expressing TLR2 failed to phagocytose these bacteria, but the cells expressing CD14 did. FSL-1 induced upregulation of the expression of phagocytic receptors including MSR1, CD36, DC-SIGN and Dectin-1 in THP-1 cells. Human embryonic kidney 293 cells transfected with DC-SIGN and MSR1 phagocytosed these bacteria. These results suggest that the FSL-1-induced enhancement of phagocytosis of bacteria by macrophages may be explained partially by the upregulation of scavenger receptors and the C-type lectins through TLR2-mediated signaling pathways and that TLR2 by itself does not function as a phagocytic receptor.
This study also demonstrated that CD14 and the C-type lectin DC-SIGN enhances the recognition of lignads by TLR2 and FSL-1 induced Th2 response in vivo.
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