RRC ID 39597
著者 Iwami KI, Matsuguchi T, Masuda A, Kikuchi T, Musikacharoen T, Yoshikai Y.
タイトル Cutting edge: naturally occurring soluble form of mouse Toll-like receptor 4 inhibits lipopolysaccharide signaling.
ジャーナル J Immunol
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-alpha production and NF-kappaB 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.
巻・号 165(12)
ページ 6682-6
公開日 2000-12-15
DOI 10.4049/jimmunol.165.12.6682
PMID 11120784
MeSH Alternative Splicing / immunology Animals Base Sequence CHO Cells Cell Line Cloning, Molecular Cricetinae DNA, Complementary / isolation & purification Drosophila Proteins* Humans Lipopolysaccharides / antagonists & inhibitors* Lipopolysaccharides / pharmacology* Macrophages / metabolism Membrane Glycoproteins / genetics Membrane Glycoproteins / isolation & purification Membrane Glycoproteins / physiology* Mice Molecular Sequence Data Molecular Weight NF-kappa B / antagonists & inhibitors NF-kappa B / metabolism RNA, Messenger / biosynthesis Receptors, Cell Surface / genetics Receptors, Cell Surface / isolation & purification Receptors, Cell Surface / physiology* Signal Transduction / immunology* Solubility T-Lymphocytes / metabolism Toll-Like Receptor 4 Toll-Like Receptors Tumor Necrosis Factor-alpha / antagonists & inhibitors Tumor Necrosis Factor-alpha / biosynthesis
IF 4.886
引用数 196
WOS 分野 IMMUNOLOGY
リソース情報
ヒト・動物細胞 RAW 264(RCB0535)