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Human Toll-like Receptor 2 Confers Responsiveness to Bacterial Lipopolysaccharide

Bacterial lipopolysaccharide (LPS) induces activation of the transcription factor nuclear factor κB (NF-κB) 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...

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Detalles Bibliográficos
Autores principales: Kirschning, Carsten J., Wesche, Holger, Merrill Ayres, T., Rothe, Mike
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1998
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212382/
https://www.ncbi.nlm.nih.gov/pubmed/9841923
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author Kirschning, Carsten J.
Wesche, Holger
Merrill Ayres, T.
Rothe, Mike
author_facet Kirschning, Carsten J.
Wesche, Holger
Merrill Ayres, T.
Rothe, Mike
author_sort Kirschning, Carsten J.
collection PubMed
description Bacterial lipopolysaccharide (LPS) induces activation of the transcription factor nuclear factor κB (NF-κB) 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-κB 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-κB signaling cascade. These findings suggest that TLR2 may be a signaling component of a cellular receptor for LPS.
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spelling pubmed-22123822008-04-16 Human Toll-like Receptor 2 Confers Responsiveness to Bacterial Lipopolysaccharide Kirschning, Carsten J. Wesche, Holger Merrill Ayres, T. Rothe, Mike J Exp Med Articles Bacterial lipopolysaccharide (LPS) induces activation of the transcription factor nuclear factor κB (NF-κB) 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-κB 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-κB signaling cascade. These findings suggest that TLR2 may be a signaling component of a cellular receptor for LPS. The Rockefeller University Press 1998-12-07 /pmc/articles/PMC2212382/ /pubmed/9841923 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Kirschning, Carsten J.
Wesche, Holger
Merrill Ayres, T.
Rothe, Mike
Human Toll-like Receptor 2 Confers Responsiveness to Bacterial Lipopolysaccharide
title Human Toll-like Receptor 2 Confers Responsiveness to Bacterial Lipopolysaccharide
title_full Human Toll-like Receptor 2 Confers Responsiveness to Bacterial Lipopolysaccharide
title_fullStr Human Toll-like Receptor 2 Confers Responsiveness to Bacterial Lipopolysaccharide
title_full_unstemmed Human Toll-like Receptor 2 Confers Responsiveness to Bacterial Lipopolysaccharide
title_short Human Toll-like Receptor 2 Confers Responsiveness to Bacterial Lipopolysaccharide
title_sort human toll-like receptor 2 confers responsiveness to bacterial lipopolysaccharide
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212382/
https://www.ncbi.nlm.nih.gov/pubmed/9841923
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