CD14 directly binds to triacylated lipopeptides and facilitates recognition of the lipopeptides by the receptor complex of Toll-like receptors 2 and 1 without binding to the complex
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概要
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It has demonstrated that the recognition of triacylated lipopeptides by Toll-like receptor (TLR) 2 requires TLR1 as a coreceptor. In the NF-κB reporter assay system in which human embryonic kidney 293 cells were transfected with TLR2 and TLR1 together with an NF-κB luciferase reporter gene, S-(2,3-bispalmitoyloxypropyl)-N-palmitoyl-Cys-Lys-Lys-Lys-Lys (Pam3CSK4) and Pam3CSSNA were recognized by TLR2/TLR1, but the recognition level was unexpectedly very low. However, cotransfection of CD14 drastically enhanced the recognition of triacylated lipopeptides by TLR2/TLR1. The CD14-induced enhancement did not occur without cotransfection of TLR1. Both CD14dS39-A48, a mutant with deletion of the part of possible N-terminal ligand-binding pocket, and anti-CD14 monoclonal antibody reduced the CD14-induced enhancement. Transfection of a TIR domain-deficient mutant of TLR2 (TLR2dE772-S784) or TLR1 (TLR1dQ636-K779) completely abrogated the CD14-induced enhancement. Soluble recombinant CD14 added extracellularly enhanced the recognition of Pam3CSSNA by TLR2/TLR1. Immunoprecipitation analysis demonstrated that CD14 was not associated with TLR2 but that TLR1 was associated with TLR2. In addition, surface plasmon resonance-based assay demonstrated that CD14 binds to Pam3CSK4 at a dissociation constant of 5.7 µM. This study suggests that CD14 directly binds to triacylated lipopeptides and facilitates recognition of the lipopeptides by the TLR2/TLR1 complex without binding to the receptor complex.
- Blackwell Publishingの論文
著者
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Sano Hidehiko
Department Of Operative Dentistry Hokkaido University School Of Dentistry
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Sano Hidehiko
Department Of Oral Health Science Hokkaido University Graduate School Of Dental Medicine
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Sano Hidehiko
Department Of Operative Dentistry Tokyo Medical And Dental University
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Sano Hidehiko
Department Of Operative Dentistry Hokkaido University Dental School
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Shibata K
Department Of Oral Pathobiological Science Hokkaido University Graduate School Of Dental Medicine
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Shibata Ken-ichiro
Division Of Oral Molecular Microbiology Department Of Oral Pathobiological Science Hokkaido Universi
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Kiura Kazuto
Division Of Oral Molecular Microbiology Department Of Oral Pathobiological Science Hokkaido Universi
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