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Soluble Heparan Sulfate Fragments Generated by Heparanase Trigger the Release of Pro-Inflammatory Cytokines through TLR-4

Overview of attention for article published in PLOS ONE, October 2014
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (90th percentile)
  • High Attention Score compared to outputs of the same age and source (87th percentile)

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1 news outlet
blogs
1 blog
twitter
1 X user

Citations

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190 Dimensions

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104 Mendeley
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Title
Soluble Heparan Sulfate Fragments Generated by Heparanase Trigger the Release of Pro-Inflammatory Cytokines through TLR-4
Published in
PLOS ONE, October 2014
DOI 10.1371/journal.pone.0109596
Pubmed ID
Authors

Katharine J. Goodall, Ivan K. H. Poon, Simon Phipps, Mark D. Hulett

Abstract

Heparanase is a β-D-endoglucuronidase that cleaves heparan sulfate (HS), facilitating degradation of the extracellular matrix (ECM) and the release of HS-bound biomolecules including cytokines. The remodeling of the ECM by heparanase is important for various physiological and pathological processes, including inflammation, wound healing, tumour angiogenesis and metastasis. Although heparanase has been proposed to facilitate leukocyte migration through degradation of the ECM, its role in inflammation by regulating the expression and release of cytokines has not been fully defined. In this study, the role of heparanase in regulating the expression and release of cytokines from human and murine immune cells was examined. Human peripheral blood mononuclear cells treated ex vivo with heparanase resulted in the release of a range of pro-inflammatory cytokines including IL-1β, IL-6, IL-8, IL-10 and TNF. In addition, mouse splenocytes treated ex vivo with heparanase resulted in the release of IL-6, MCP-1 and TNF. A similar pattern of cytokine release was also observed when cells were treated with soluble HS. Furthermore, heparanase-induced cytokine release was abolished by enzymatic-inhibitors of heparanase, suggesting this process is mediated via the enzymatic release of cell surface HS fragments. As soluble HS can signal through the Toll-like receptor (TLR) pathway, heparanase may promote the upregulation of cytokines through the generation of heparanase-cleaved fragments of HS. In support of this hypothesis, mouse spleen cells lacking the key TLR adaptor molecule MyD88 demonstrated an abolition of cytokine release after heparanase stimulation. Furthermore, TLR4-deficient spleen cells showed reduced cytokine release in response to heparanase treatment, suggesting that TLR4 is involved in this response. Consistent with these observations, the pathway involved in cytokine upregulation was identified as being NF-κB-dependent. These data identify a new mechanism for heparanase in promoting the release of pro-inflammatory cytokines that is likely to be important in regulating cell migration and inflammation.

X Demographics

X Demographics

The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 104 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Czechia 1 <1%
Germany 1 <1%
Australia 1 <1%
Unknown 101 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 20 19%
Researcher 15 14%
Student > Bachelor 13 13%
Student > Master 10 10%
Other 8 8%
Other 18 17%
Unknown 20 19%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 26 25%
Agricultural and Biological Sciences 15 14%
Medicine and Dentistry 13 13%
Immunology and Microbiology 11 11%
Chemistry 6 6%
Other 10 10%
Unknown 23 22%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 15. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 June 2023.
All research outputs
#2,190,631
of 23,928,031 outputs
Outputs from PLOS ONE
#27,347
of 205,374 outputs
Outputs of similar age
#25,062
of 258,640 outputs
Outputs of similar age from PLOS ONE
#664
of 5,250 outputs
Altmetric has tracked 23,928,031 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 90th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 205,374 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.5. This one has done well, scoring higher than 86% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 258,640 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 90% of its contemporaries.
We're also able to compare this research output to 5,250 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 87% of its contemporaries.