Cell activation by Porphyromonas gingivalis lipid A molecule through Toll-like receptor 4- and myeloid differentiation factor 88- dependent signaling pathway

Tomohiko Ogawa, Yasuyuki Asai, Masahito Hashimoto, Osamu Takeuchi, Tomoko Kurita, Yasunobu Yoshikai, Kensuke Miyake, Shizuo Akira

    Research output: Contribution to journalArticlepeer-review

    107 Citations (Scopus)

    Abstract

    Porphyromonas gingivalis lipopolysaccharide (LIPS) and its bioactive center, lipid A, are known to exhibit very low endotoxic activities and activate LPS-hyporesponsive C3H/HaJ mice that have a point mutation in the cytoplasmic portion of Toll-like receptor (TLR) 4, in contrast to classical enterobacterial LIPS and their lipid A. In the present study, we attempted to determine which TLR mediates the response to lipid A from A gingivalis strain 381. P. gingivalis LIPS and its natural lipid A fraction induced NF-κB activation primarily in Ba/F3 cells expressing mouse TLR 2 (Ba/mTLR2), rather than in those expressing mouse TLR4 and its accessory protein MD2 (Ba/mTLR4/mMD2). Further purification of the natural lipid A fraction resulted in a significant decrease of NF-κB activation in Ba/mTLR2, although not in Ba/mTLR4/mMD2. The synthetic counterpart of P. gingivalis strain 381-lipid A (compound PG-381) also elicited NF-κB activation in Ba/mTLR4/mMD2, but not Ba/mTLR2. Furthermore, P. gingivalis purified natural lipid A and compound PG-381 lacked the ability to activate gingival fibroblasts from C3H/HeJ, TILR4 knockout (KO) and myeloid differentiation factor 88 (MyD88) KO mice. These findings demonstrate that the P. gingivalis lipid A molecule induces cell activation via a TLR4/MD2-MyD88-dependent pathway, and suggest the possibility that unknown bacterial components in P. gingivalis LPS and its lipid A may induce cell activation via TLR2.

    Original languageEnglish
    Pages (from-to)1325-1332
    Number of pages8
    JournalInternational immunology
    Volume14
    Issue number11
    DOIs
    Publication statusPublished - Nov 1 2002

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology

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