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Oligosaccharides of Hyaluronan Activate Dendritic Cells via Toll-like Receptor 4
Low molecular weight fragmentation products of the polysaccharide of Hyaluronic acid (sHA) produced during inflammation have been shown to be potent activators of immunocompetent cells such as dendritic cells (DCs) and macrophages. Here we report that sHA induces maturation of DCs via the Toll-like...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2002
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196009/ https://www.ncbi.nlm.nih.gov/pubmed/11781369 http://dx.doi.org/10.1084/jem.20001858 |
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author | Termeer, Christian Benedix, Frauke Sleeman, Jonathon Fieber, Christina Voith, Ursula Ahrens, Thomas Miyake, Kensuke Freudenberg, Marina Galanos, Christopher Simon, Jan Christoph |
author_facet | Termeer, Christian Benedix, Frauke Sleeman, Jonathon Fieber, Christina Voith, Ursula Ahrens, Thomas Miyake, Kensuke Freudenberg, Marina Galanos, Christopher Simon, Jan Christoph |
author_sort | Termeer, Christian |
collection | PubMed |
description | Low molecular weight fragmentation products of the polysaccharide of Hyaluronic acid (sHA) produced during inflammation have been shown to be potent activators of immunocompetent cells such as dendritic cells (DCs) and macrophages. Here we report that sHA induces maturation of DCs via the Toll-like receptor (TLR)-4, a receptor complex associated with innate immunity and host defense against bacterial infection. Bone marrow–derived DCs from C3H/HeJ and C57BL/10ScCr mice carrying mutant TLR-4 alleles were nonresponsive to sHA-induced phenotypic and functional maturation. Conversely, DCs from TLR-2–deficient mice were still susceptible to sHA. In accordance, addition of an anti–TLR-4 mAb to human monocyte–derived DCs blocked sHA-induced tumor necrosis factor α production. Western blot analysis revealed that sHA treatment resulted in distinct phosphorylation of p38/p42/44 MAP-kinases and nuclear translocation of nuclear factor (NF)-κB, all components of the TLR-4 signaling pathway. Blockade of this pathway by specific inhibitors completely abrogated the sHA-induced DC maturation. Finally, intravenous injection of sHA-induced DC emigration from the skin and their phenotypic and functional maturation in the spleen, again depending on the expression of TLR-4. In conclusion, this is the first report that polysaccharide degradation products of the extracellular matrix produced during inflammation might serve as an endogenous ligand for the TLR-4 complex on DCs. |
format | Text |
id | pubmed-2196009 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2002 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21960092008-04-14 Oligosaccharides of Hyaluronan Activate Dendritic Cells via Toll-like Receptor 4 Termeer, Christian Benedix, Frauke Sleeman, Jonathon Fieber, Christina Voith, Ursula Ahrens, Thomas Miyake, Kensuke Freudenberg, Marina Galanos, Christopher Simon, Jan Christoph J Exp Med Original Article Low molecular weight fragmentation products of the polysaccharide of Hyaluronic acid (sHA) produced during inflammation have been shown to be potent activators of immunocompetent cells such as dendritic cells (DCs) and macrophages. Here we report that sHA induces maturation of DCs via the Toll-like receptor (TLR)-4, a receptor complex associated with innate immunity and host defense against bacterial infection. Bone marrow–derived DCs from C3H/HeJ and C57BL/10ScCr mice carrying mutant TLR-4 alleles were nonresponsive to sHA-induced phenotypic and functional maturation. Conversely, DCs from TLR-2–deficient mice were still susceptible to sHA. In accordance, addition of an anti–TLR-4 mAb to human monocyte–derived DCs blocked sHA-induced tumor necrosis factor α production. Western blot analysis revealed that sHA treatment resulted in distinct phosphorylation of p38/p42/44 MAP-kinases and nuclear translocation of nuclear factor (NF)-κB, all components of the TLR-4 signaling pathway. Blockade of this pathway by specific inhibitors completely abrogated the sHA-induced DC maturation. Finally, intravenous injection of sHA-induced DC emigration from the skin and their phenotypic and functional maturation in the spleen, again depending on the expression of TLR-4. In conclusion, this is the first report that polysaccharide degradation products of the extracellular matrix produced during inflammation might serve as an endogenous ligand for the TLR-4 complex on DCs. The Rockefeller University Press 2002-01-07 /pmc/articles/PMC2196009/ /pubmed/11781369 http://dx.doi.org/10.1084/jem.20001858 Text en Copyright © 2002, The Rockefeller University Press 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 | Original Article Termeer, Christian Benedix, Frauke Sleeman, Jonathon Fieber, Christina Voith, Ursula Ahrens, Thomas Miyake, Kensuke Freudenberg, Marina Galanos, Christopher Simon, Jan Christoph Oligosaccharides of Hyaluronan Activate Dendritic Cells via Toll-like Receptor 4 |
title | Oligosaccharides of Hyaluronan Activate Dendritic Cells via Toll-like Receptor 4 |
title_full | Oligosaccharides of Hyaluronan Activate Dendritic Cells via Toll-like Receptor 4 |
title_fullStr | Oligosaccharides of Hyaluronan Activate Dendritic Cells via Toll-like Receptor 4 |
title_full_unstemmed | Oligosaccharides of Hyaluronan Activate Dendritic Cells via Toll-like Receptor 4 |
title_short | Oligosaccharides of Hyaluronan Activate Dendritic Cells via Toll-like Receptor 4 |
title_sort | oligosaccharides of hyaluronan activate dendritic cells via toll-like receptor 4 |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196009/ https://www.ncbi.nlm.nih.gov/pubmed/11781369 http://dx.doi.org/10.1084/jem.20001858 |
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