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Human Toll-like receptor 2 confers responsiveness to bacterial lipopolysaccharide (1998)
| Citations: | 98 - 4 self |
BibTeX
@MISC{Kirschning98humantoll-like,
author = {J. Kirschning and Holger Wesche and T. Merrill Ayres and Mike Rothe},
title = {Human Toll-like receptor 2 confers responsiveness to bacterial lipopolysaccharide},
year = {1998}
}
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Abstract
Bacterial lipopolysaccharide (LPS) induces activation of the transcription factor nuclear factor �B (NF-�B) in host cells upon infection. LPS binds to the glycosylphosphatidylinositol (GPI)anchored membrane protein CD14, which lacks an intracellular signaling domain. Here we investigated the role of mammalian Toll-like receptors (TLRs) as signal transducers for LPS. Overexpression of TLR2, but not TLR1, TLR4, or CD14 conferred LPS inducibility of NF-�B activation in mammalian 293 cells. Mutational analysis demonstrated that this LPS response requires the intracellular domain of TLR2. LPS signaling through TLR2 was dependent on serum which contains soluble CD14 (sCD14). Coexpression of CD14 synergistically enhanced LPS signal transmission through TLR2. In addition, purified recombinant sCD14 could substitute for serum to support LPS-induced TLR2 activation. LPS stimulation of TLR2 initiated an interleukin 1 receptor–like NF-�B signaling cascade. These findings suggest that TLR2 may be a signaling component of a cellular receptor for LPS. Key words: lipopolysaccharide • CD14 • interleukin 1 receptor • nuclear factor �B • signal transduction Bacterial LPS (also known as endotoxin), a constituent
Keyphrases
bacterial lipopolysaccharide human toll-like receptor nf activation lipopolysaccharide cd14 recombinant scd14 lp stimulation lp response key word transcription factor nuclear factor mutational analysis soluble cd14 signal transducer membrane protein cd14 lp inducibility intracellular domain intracellular signaling domain lp signal transmission host cell cellular receptor lps-induced tlr2 activation mammalian toll-like receptor signaling component
