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In vivo protection provided by a synthetic new alpha-galactosyl ceramide analog against bacterial and viral infections in murine models

Academic Article
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Overview

authors

  • Lin, K. H.
  • Liang, J. J.
  • Huang, W. I.
  • Lin-Chu, S. Y.
  • Su, C. Y.
  • Lee, Y. L.
  • Jan, J. T.
  • Lin, Y. L.
  • Cheng, Y. S. E.
  • Wong, Chi-Huey

publication date

  • October 2010

journal

  • Antimicrobial Agents and Chemotherapy  Journal

abstract

  • Alpha-galactosyl ceramide (α-GalCer) has been known to bind to the CD1d receptor on dendritic cells and activate invariant natural killer T (iNKT) cells, which subsequently secrete T-helper-cell 1 (Th1) and Th2 cytokines, which correlate with anti-infection activity and the prevention of autoimmune diseases, respectively. α-GalCer elicits the secretion of these two cytokines nonselectively, and thus, its effectiveness is limited by the opposing effects of the Th1 and Th2 cytokines. Reported here is the synthesis of a new α-GalCer analog (compound C34), based on the structure of CD1d, with a 4-(4-fluorophenoxy) phenyl undecanoyl modification of the N-acyl moiety of α-GalCer. Using several murine bacterial and viral infection models, we demonstrated that C34 has superior antibacterial and antiviral activities in comparison with those of several other Th1-selective glycolipids and that it is most effective by administering it to mice in a prophylactic manner before or shortly after infection.

subject areas

  • Animals
  • Anti-Bacterial Agents
  • Female
  • Galactosylceramides
  • Gram-Negative Bacterial Infections
  • Mice
  • Mice, Inbred BALB C
  • Sphingomonas
  • Staphylococcus aureus
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Identity

PubMed Central ID

  • PMC2944612

International Standard Serial Number (ISSN)

  • 0066-4804

Digital Object Identifier (DOI)

  • 10.1128/aac.00368-10

PubMed ID

  • 20660669
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Additional Document Info

start page

  • 4129

end page

  • 4136

volume

  • 54

issue

  • 10

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