Dissociation of Toll-Like Receptor 2-Mediated Innate Immune Response to Zymosan by Organic Solvent-Treatment without Loss of Dectin-1 Reactivity

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Author(s)

    • MIURA Noriko
    • Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
    • OHNO Naohito
    • Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences

Abstract

Zymosan activates phagocytes through the innate immune system and causes inflammatory responses in animals. Because of the complexity of the active substances included in Zymosan preparations, simplifying the active moiety actually responsible for innate immune recognition is needed. One way to remove possible active substances from commercially available Zymosan preparations is to wash then with pyrogen-free water to obtain a ZWIS (Zymosan water insoluble fraction), ethanol insoluble (EtIS), or chloroform/methanol insoluble (CMIS) preparation. The effects of various washed Zymosan preparations on nuclear factor (NF)-κB activation and binding to β-glucan recognition protein were examined. Significant NF-κB activation by Toll-like receptor (TLR) 2-expressing HEK293 cells and enhanced NF-κB activity <i>via</i> the co-expression of TLR2 and Dectin-1, a functional β-glucan receptor, was only observed in response to ZWIS. However, the ability of Zymosan preparations to bind Dectin-1 protein was not altered even after treatment with the organic solvents by which the TLR2-mediated NF-κB activity was abolished. Another NF-κB activation pathway involving CARD9/Bcl10 was triggered by these Zymosan preparations in the presence of Dectin-1. The results suggest that the β-glucan-dependent characteristics of Zymosan were not affected by the washing with chloroform/methanol or ethanol, and that TLR2-mediated activity was easily eliminated with these organic solvents. This treatment might be useful for distinguishing natural ligands for TLR2 and β-glucan receptors when studying the innate immune response to fungal macromolecules.

Journal

  • Biological and Pharmaceutical Bulletin

    Biological and Pharmaceutical Bulletin 31(1), 13-18, 2008-01-01

    The Pharmaceutical Society of Japan

References:  32

Codes

  • NII Article ID (NAID)
    110006569967
  • NII NACSIS-CAT ID (NCID)
    AA10885497
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    09186158
  • NDL Article ID
    9312114
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-V41
  • Data Source
    CJP  NDL  NII-ELS  J-STAGE 
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