Studies on recognition mechanism of oral microbes-derived lipopeptides by Toll-like receptors
| Project/Area Number |
15390549
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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 |
Morphological basic dentistry
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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) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 2004: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2003: ¥9,700,000 (Direct Cost: ¥9,700,000)
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| Keywords | Toll-like receptor 2 / lipopeptides / lipopeoteins / Leucine-rich repeats / apoptosis / Toll-like receptor / ペプチドグリカン / Toll様受容体 |
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| Research Abstract |
Toll-like receptor 2 (TLR2)plays a key role in the recognition of microbial lipoproteins/lipoeppetides. However, details in molecular mechanisms of the recognition still remains unknown. This study was therefore carried out to determine the molecular mechanism by which TLR2 recognizes microbial lipoproteins/lipoeppetides.
We have found the following findings.
1.The level of the activity of bacterial triacylated lipopeptides to stimulate macrophages was lower than that of mycoplasmal diacylated lipoepptides.
2.Both lipid and peptide portions of mycoplasmal diacylated lipopeptides are involved in the recognition by TLR2.
3.Leucine residues at positions 107,112 and 115 are involved in the recognition of mycoplasmal lipoproteins/lipopeptide and S.aureus peptidoglycans by TLR2 in combination with TLR6.
4.There is at least one leucine residue in all 8 leucine-rich repeats of TLR2 which is responsible for the the recognition of mycoplasmal lipoproteins/lipopeptide and S.aureus peptidoglycans by TLR2 in combination with TLR6.
5.Leucine residues in β-sheet structure of leucine-rich repeats are involved in the recognition of mycoplasmal lipopeptides by TLR2 in combination with TLR6.
6.Mycoplasmal lipoproteins possesses the activity to induce apoptosis of HEK293 cells through TLR2/TLR2 and the activity is mediated by FADD and MyD88 downstream of TLR2.
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Report
(3 results)
Research Products
(20 results)
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[Journal Article] Relationship between structures and biological activities of mycoplasmal diacylated lipopeptides and their recognition by Toll-like receptors 2 and 6.2004
Author(s)
T Okusawa, M Fujita, J Nakamura, T Into, M Yasuda, A Yoshimura, Y Hara, A Hasebe, DT Golenbock, M Morita, Y Kuroki, T Ogawa, K Shibata.
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Journal Title
Infect Immun 72(3)
Pages: 1657-1665
NAID
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Biological activities of Bacteroides forsythus lipoproteins and their possible pathological roles in periodontal disease.2004
Author(s)
A Hasebe, A Yoshimura, T Into, H Kataoka, S Tanaka, S Arakawa, H Ishikura, DT Golenbock, T Sugaya, N Tsuchida, M Kawanami, Y Hara, K Shibata
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Journal Title
Infect Immun 72(3)
Pages: 1318-1325
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Involvement of leucine residues at positions 107,112 and 115 in a leucine-rich repeat motif of human Toll-like receptor 2 in the recognition of diacylated lipoproteins and lipopeptides and Staphylococcus aureus peptidoglycans.2003
Author(s)
M Fujita, T Into, M Yasuda, T Okusawa, S Hamahira, Y Kuroki, A Eto, T Nisizawa, M Morita, K Shibata.
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Journal Title
J Immunol. 171
Pages: 3675-3683
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Involvement of leucine residues at positions 107,112 and 115 in a leucine-rich repeat motif of human Toll-like receptor 2 in the recognition of diacylated lipoproteins and liopeptides and Staphylococcus aureus peptidoglycans2003
Author(s)
M.Fujita, T.Into, M.Yasuda, T.Okusawa, S.Hamahira, Y.Kuroki, A.Eto, T.Nisizawa, M.Morita, K.Shibata.
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Journal Title
Journal of Immunology 171
Pages: 3675-3683
Related Report
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[Publications] M.Fujita, T.Into, M.Yasuda, T.Okusawa, S.Hamahira, Y.Kuroki, A.Eto, T.Nisizawa, M.Morita, K.Shibata: "Involvement of leucine residues at positions 107, 112 and 115 in a leucine-rich repeat motif of human toll-like receptor 2 in the recognition of diacylated lipoproteins and lipopeptides and Staphylococcus aureus peptidoglycans"Journal of Immunology. 171. 3675-3683 (2003)
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