Cutting edge: Naturally occurring soluble form of mouse toll-like receptor 4 inhibits lipopolysaccharide signaling

K. I. Iwami, T. Matsuguchi, A. Masuda, T. Kikuchi, T. Musikacharoen, Y. Yoshikai

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    197 Citations (Scopus)

    Abstract

    Toll-like receptors (TLRs) are a family of proteins playing important roles in host defense. Mice defective of functional TLR4 are hyporesponsive to LPS, suggesting that TLR4 is essential for LPS signaling. Here we report the cloning of an alternatively spliced mouse TLR4 (mTLR4) mRNA. The additional exon exists between the second and third exon of the reported mTLR4 gene and contains an in-frame stop codon. The alternatively spliced mRNA encodes 86 aa of the reported mTLR4 and an additional 36 aa. This alternatively spliced mTLR4 mRNA expressed a partially secretary 20-kDa protein, which we named soluble mTLR4 (smTLR4). In a mouse macrophage cell line, the exogenously expressed smTLR4 significantly inhibited LPS-mediated TNF-α production and NF-κB activation. Additionally, in mouse macrophages, LPS increased the mRNA for smTLR4. Taken together, our results indicate that smTLR4 may function as a feedback mechanism to inhibit the excessive LPS responses in mouse macrophages.

    Original languageEnglish
    Pages (from-to)6682-6686
    Number of pages5
    JournalJournal of Immunology
    Volume165
    Issue number12
    DOIs
    Publication statusPublished - Dec 15 2000

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    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology

    Cite this

    Iwami, K. I., Matsuguchi, T., Masuda, A., Kikuchi, T., Musikacharoen, T., & Yoshikai, Y. (2000). Cutting edge: Naturally occurring soluble form of mouse toll-like receptor 4 inhibits lipopolysaccharide signaling. Journal of Immunology, 165(12), 6682-6686. https://doi.org/10.4049/jimmunol.165.12.6682