Hyaluronan Fragments Act as an Endogenous Danger Signal by Engaging TLR2
Open accessAbstract
Upon tissue injury, high m.w. hyaluronan (HA), a ubiquitously distributed extracellular matrix component, is broken down into lower m.w. (LMW) fragments, which in turn activate an innate immune response. In doing so, LMW HA acts as an endogenous danger signal alerting the immune system of a breach in tissue integrity. In this report, we demonstrate that LMW HA activates the innate immune response via TLR-2 in a MyD88-, IL-1R-associated kinase-, TNFR-associated factor-6-, protein kinase Cζ-, and NF-κB-dependent pathway. Furthermore, we show that intact high m.w. HA can inhibit TLR-2 signaling. Finally, we demonstrate that LMW HA can act as an adjuvant promoting Ag-specific T cell responses in vivo in wild-type but not TLR-2null mice.
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There is evidence for a role of TLR2 and/or TLR4 in the induction of cytokine and chemokine production in response to extracellular matrix components, including hyaluronan fragments or soluble proteoglycan components, in vitro and in vivo.
“For example, there is evidence for a role of TLR2 and/or TLR4 in the induction of cytokine and chemokine production in response to extracellular matrix components, including hyaluronan fragments or soluble proteoglycan components, in vitro and in vivo31–34.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [32]
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- Authors
- Scheibner, K. A., Lutz, M. A., Boodoo, S., Fenton, M. J., Powell, J. D., & Horton, M. R.
- Affiliations
- Johns Hopkins University (US)
- University of Maryland, Baltimore (US)
- Corresponding author
- Boodoo, Sada
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-07
- Volume
- 177
- Issue
- 2
- Pages
- 1272-1281
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2144032514
- Cited by
- 708
- References
- 57
- Citations by year
- 2026: 20 · 2025: 26 · 2024: 22 · 2023: 28 · 2022: 26 · 2021: 38 · 2020: 49 · 2019: 43 · 2018: 38 · 2017: 31 · 2016: 35 · 2015: 39 · 2014: 52 · 2013: 42 · 2012: 33
- FWCI
- 13.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cedars-Sinai Medical Center
- National Heart, Lung, and Blood Institute (R01-HL-0961402, R01HL073855)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Keywords
- hyaluronan fragments, low molecular weight hyaluronic acid, TLR2, endogenous danger signals, innate immunity, tissue damage, MyD88, TRAF6, NF-κB, protein kinase C zeta, adjuvants, T cell response, extracellular matrix
- MeSH terms
- Protein Kinase C zeta, Adjuvants, Immunologic, Animals, Cell Line, Female, Gene Expression Regulation, Humans, Hyaluronic Acid, Isoenzymes, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Transgenic, Molecular Weight, Protein Kinase C, Signal Transduction, Mice, Knockout, Inflammation Mediators, Adaptor Proteins, Signal Transducing, Toll-Like Receptor 2, Mice, Myeloid Differentiation Factor 88
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