The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Oligosaccharides of Hyaluronan Activate Dendritic Cells via Toll-like Receptor 4
Open accessAbstract
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.
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“ECM-bioscaffold degradation products function as damage-associated molecular patterns (DAMPs) that ligate pattern-recognition and scavenger receptors on dendritic cells and macrophages; in some contexts, they also signal via integrins [2,26,28,29].”
From Immune Response to Extracellular Matrix Bioscaffolds: A Comprehensive Review (2025) · cites this paper as [28]
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Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in Tlr4 Gene
Poltorak, A., He, X., Smirnova, I., Liu, M.-Y., Huffel, C. V., Du, X., Birdwell, D., Alejos, E., Silva, M., Galanos, C., et al. (1998) · Science · doi:10.1126/science.282.5396.2085 · Cited by 7,631
Self-citationTakeuchi, O., Hoshino, K., Kawai, T., Sanjo, H., Takada, H., Ogawa, T., Takeda, K., & Akira, S. (1999) · Immunity · doi:10.1016/s1074-7613(00)80119-3 · Cited by 3,680
Alessi, D. R., Cuenda, A., Cohen, P., Dudley, D. T., & Saltiel, A. R. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.46.27489 · Cited by 3,374
Toll-like receptors in the induction of the innate immune response
Aderem, A. A., & Ulevitch, R. J. (2000) · Nature · doi:10.1038/35021228 · Cited by 3,082
MD-2, a Molecule that Confers Lipopolysaccharide Responsiveness on Toll-like Receptor 4
Shimazu, R., Akashi, S., Ogata, H., Nagai, Y., Fukudome, K., Miyake, K., & Kimoto, M. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.189.11.1777 · Cited by 2,187
Self-citationA family of human receptors structurally related to Drosophila Toll.
Rock, F., Hardiman, G., Timans, J., Kastelein, R., & Bazan, J. (1998) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.95.2.588 · Cited by 2,009
Laurent, T. C., & Fraser, J. R. E. (1992) · The FASEB Journal · doi:10.1096/fasebj.6.7.1563592 · Cited by 2,004
MyD88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways.
Medzhitov, R., Preston-Hurlburt, P., Kopp, E., Stadlen, A., Chen, C.-Q., Ghosh, S., & Janeway, C. (1998) · Molecules and Cells · doi:10.1016/s1097-2765(00)80136-7 · Cited by 1,783
Ohashi, K., Burkart, V., Flohé, S. B., & Kolb, H. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.2.558 · Cited by 1,607
Toll-like Receptor 2 Functions as a Pattern Recognition Receptor for Diverse Bacterial Products*
Lien, E., Sellati, T., Yoshimura, A., Flo, T., Rawadi, G., Finberg, R., Carroll, J. D., Espevik, T., Ingalls, R., Radolf, J., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.47.33419 · Cited by 1,062
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Research works printed but not linked: 5
- 1998, Lab. Invest., 78, 987
- 2000, Chem. Immunol., 74, 61
- 1991, Cancer Res., 51, 2524
- 1999, Cancer Res., 59, 1287
- 1994, Cancer Res., 54, 2419
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Immune Response to Extracellular Matrix Bioscaffolds: A Comprehensive Review
Romero, D. J., Hussey, G., & Capella-Monsonís, H. (2025) · Biologics · doi:10.3390/biologics5030028 · Cited by 7
“ECM-bioscaffold degradation products function as damage-associated molecular patterns (DAMPs) that ligate pattern-recognition and scavenger receptors on dendritic cells and macrophages; in some contexts, they also signal via integrins [2,26,28,29].”
Metadata
- Authors
- Termeer, C., Benedix, F., Sleeman, J., Fieber, C., Voith, U., Ahrens, T., Miyake, K., Freudenberg, M., Galanos, C., & Simon, J. C.
- Affiliations
- University of Freiburg (DE)
- 2Institute for Genetics, Forschungszentrum Karlsruhe, Karlsruhe D-76021, Germany
- University of Basel (CH)
- Institute of Medical Science, The University of Tokyo (JP)
- Max Planck Society (DE)
- 3Max-Planck Institute for Immunobiology, Freiburg D-79011, Germany
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2002-01-07
- Volume
- 195
- Issue
- 1
- Pages
- 99-111
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2196009
- OpenAlex
- W2126659405
- Semantic Scholar
- 44579905bd40557fb010b65248e3194bbd6a995d
- Cited by
- 1,378
- References
- 48
- Citations by year
- 2026: 19 · 2025: 29 · 2024: 28 · 2023: 28 · 2022: 32 · 2021: 54 · 2020: 46 · 2019: 40 · 2018: 40 · 2017: 41 · 2016: 54 · 2015: 59 · 2014: 71 · 2013: 61 · 2012: 69
- FWCI
- 18.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Max Planck Digital Library (submittedVersion)
- FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- hyaluronic acid, oligosaccharides, dendritic cell maturation, TLR4, TLR2, innate immunity, endogenous ligands, MAPK signaling, TNF-α, extracellular matrix degradation, inflammation
- MeSH terms
- Animals, Cell Differentiation, Dendritic Cells, Female, Humans, Hyaluronic Acid, Membrane Glycoproteins, Mice, Inbred C3H, Mice, Inbred C57BL, Oligosaccharides, Receptors, Cell Surface, Tumor Necrosis Factor-alpha, Signal Transduction, Down-Regulation, NF-kappa B, Mitogen-Activated Protein Kinases, Drosophila Proteins, Toll-Like Receptors, Toll-Like Receptor 2, Toll-Like Receptor 4, Mice
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