The TLR2 ligand FSL-1 is internalized via clathrin-dependent endocytic pathway triggered by CD14 and CD36 but not by TLR2

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概要

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• Little is known about how Toll-like receptor (TLR) ligands are processed after recognition by TLRs. This study was therefore designed to investigate how the TLR2 ligand FSL-1 is processed in macrophages after recognition by TLR2. FSL-1 was internalized into murine macrophage cell line, RAW264.7. Both chlorpromazine and methyl-β-cyclodextrin, which inhibit clathrin-dependent endocytosis, reduced FSL-1 uptake by RAW264.7 cells in a dose-dependent manner, but nystatin which inhibits caveolae- and lipid raft-dependent endocytosis, did not. FSL-1 was colocalized with clathrin but not with TLR2 in the cytosol of RAW264.7 cells. These results suggest that internalization of FSL-1 is clathrin dependent. In addition, FSL-1 was internalized by peritoneal macrophages from TLR2-deficient mice. FSL-1 was internalized by human embryonic kidney 293 cells transfected with CD14 or CD36 but not by the non-transfected cells. Also, knockdown of CD14 or CD36 in the transfectants reduced FSL-1 uptake In this study, we suggest that (i) FSL-1 is internalized into macrophages via a clathrin-dependent endocytic pathway, (ii) the FSL-1 uptake by macrophages occurs irrespective of the presence of TLR2, and (iii) CD14 and CD36 are responsible for the 18 internalization of FSL-1.

• 2010-06-01

著者

• Shibata K

  Department Of Oral Pathobiological Science Hokkaido University Graduate School Of Dental Medicine

• Hasebe Akira

  National Institute For Agro-environmental Sciences

• Hasebe A

  Aichi Univ. Education Kariya Jpn

• Hasebe Akira

  Department Of Environmental Chemistry National Institute For Agro-environmental Sciences

• Ohtani Makoto

  Division Of Oral Molecular Microbiology Department Of Oral Pathobiological Science Hokkaido Universi

• Shibata Ken-ichiro

  Division Of Oral Molecular Microbiology Department Of Oral Pathobiological Science Hokkaido Universi

• Kiura Kazuto

  Division Of Oral Molecular Microbiology Department Of Oral Pathobiological Science Hokkaido Universi

• Hasebe Akira

  Division Of Oral Molecular Microbiology Department Of Oral Pathobiological Science Hokkaido Universi

• Totsuka Yasunori

  Division Of Oral And Maxillofacial Surgery Department Of Oral Pathobiological Science Hokkaido Unive

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