Relationship between structures and biological activities of mycoplasmal diacylated lipopeptides and their recognition by Toll-like receptors 2 and 6

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概要

• 論文の詳細を見る

• The lipopeptide FSL-1 [S-(2,3-bispalmitoyloxypropyl)-Cys-Gly-Asp-Pro-Lys-His-Pro-Lys-Ser-Phe,Pam2CGDPKHPKSF] synthesized on the basis of the N-terminal structure of a Mycoplasmasalivarium lipoprotein capable of activating normal human gingival fibroblasts to induce the cellsurface expression of ICAM-1 revealed the activity to induce production of monocytechemoattractant protein-1, IL-6 and IL-8. FSL-1 also activated macrophages to produce TNF-α asthe M. fermentans-derived lipopeptide MALP-2 (Pam2CGNNDESNISFKEK), a potentmacrophage-activating lipopeptide did. The level of the activity of FSL-1 was higher than that ofMALP-2. This result suggests that the difference in the amino acid sequence of the peptide portionaffects the activity, because the framework structure other than the amino acid sequence of theformer is the same as that of the latter. To determine minimal structural requirements for theactivity of FSL-1, the diacylglyceryl Cys and the peptideportions were examined for the activity.Both portions did not reveal the activity. A single amino acid substitution from Phe to Arg and afatty acid substitution from palmitic acid to stearic acid drastically reduced the activity. The similarresults were obtained by the NF-κB reporter activity of FSL-1 to human embryonic kidney (HEK)293 cells transfected with Toll-like receptor 2 and 6 together with a NF-κB dependent luciferasereporter plasmid.These results suggest that both the diacylglyceryl and peptide portions of FSL-1 areindispensable for the expression of biological activities and for the recognition by Toll-likereceptors 2 and 6, and that the recognition of FSL-1 by Toll-like receptors 2 and 6 appears to be hydrophobic.

• American Society for Microbiologyの論文

著者

• Yoshimura A

  Department Of Periodontology Nagasaki University School Of Dentistry

• YOSHIMURA Atsutoshi

  Division of Periodontology, Nagasaki University Graduate School of Biomedical Sciences

• GOLENBOCK Douglas

  Division of Infectious Diseases and Immunology, University of Massachusetts, Medical School

• HARA Yoshitaka

  Division of Periodontology, Nagasaki University Graduate School of Biomedical Sciences

• Shibata K

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

• Fujita Mari

  Department Of Oral Health 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

• Morita Manabu

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

• Hara Yoshitaka

  Division Of Periodontology Nagasaki University Graduate School Of Biomedical Sciences

• Yoshimura Atsutoshi

  Division Of Periodontology Nagasaki University Graduate School Of Biomedical Sciences

• Golenbock Douglas

  Division Of Infectious Diseases And Immunology University Of Massachusetts Medical School

• Shibata Ken-ichiro

  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

• Shibata Ken-ichiro

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

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