Evidence map›Paper›PMID 27869206›Full record

ArticleScientific reports2016

Endotoxin free hyaluronan and hyaluronan fragments do not stimulate TNF-α, interleukin-12 or upregulate co-stimulatory molecules in dendritic cells or macrophages.

Yifei Dong, Arif Arif, Mia Olsson, Valbona Cali, Blair Hardman, Manisha Dosanjh, Mark Lauer, Ronald J Midura, Vincent C Hascall, Kelly L Brown and 1 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
5.7field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

47 citing papers in PubMed, 80 citations in OpenAlex.

  1. Article
  2. Hyaluronan in cardiac disease: implications for the extracellular matrix beyond collagen.American journal of physiology. Heart and circulatory physiology · 2026
    Review
  3. Review
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  5. Review
  6. Article
  7. Article
  8. Hyaluronan: An Architect and Integrator for Cancer and Neural Diseases.International journal of molecular sciences · 2025
    Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Hyaluronan in the pathogenesis of acute and post-acute COVID-19 infection.Matrix biology : journal of the International Society for Matrix Biology · 2023
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Biobridge: An Outlook on Translational Bioinks for 3D Bioprinting.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Yifei DongDepartment of Microbiology and Immunology, University of British Columbia, Vancouver, B.C. V6T 1Z3, Canada.
Arif ArifDepartment of Microbiology and Immunology, University of British Columbia, Vancouver, B.C. V6T 1Z3, Canada.
Mia OlssonDepartment of Microbiology and Immunology, University of British Columbia, Vancouver, B.C. V6T 1Z3, Canada.
Valbona CaliDepartment of Biomedical Engineering, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio 44195, U.S.A.
Blair HardmanDepartment of Microbiology and Immunology, University of British Columbia, Vancouver, B.C. V6T 1Z3, Canada.
Manisha DosanjhDepartment of Microbiology and Immunology, University of British Columbia, Vancouver, B.C. V6T 1Z3, Canada.
Mark LauerDepartment of Biomedical Engineering, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio 44195, U.S.A.
Ronald J MiduraDepartment of Biomedical Engineering, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio 44195, U.S.A.
Vincent C HascallDepartment of Biomedical Engineering, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio 44195, U.S.A.
Kelly L BrownDepartment of Pediatrics, British Columbia Children's Hospital Research Institute, Vancouver, B.C. Canada.
Pauline JohnsonDepartment of Microbiology and Immunology, University of British Columbia, Vancouver, B.C. V6T 1Z3, Canada.
University of British Columbia · CABC Children's Hospital · CA

Funding

VERSICAN PROTEOLYSIS AND REGULATION OF VASCULAR SMOOTH MUSCLEP01HL107147 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI LAUER, MARK E · 2011 to 2017
$16.1M
CIHR MOP 119503NHLBI NIH HHS P01 HL107147
6 · The paper itself

Abstract

The extracellular matrix glycosaminoglycan, hyaluronan, has been described as a regulator of tissue inflammation, with hyaluronan fragments reported to stimulate innate immune cells. High molecular mass hyaluronan is normally present in tissues, but upon inflammation lower molecular mass fragments are generated. It is unclear if these hyaluronan fragments induce an inflammatory response or are a consequence of inflammation. In this study, mouse bone marrow derived macrophages and dendritic cells (DCs) were stimulated with various sizes of hyaluronan from different sources, fragmented hyaluronan, hyaluronidases and heavy chain modified-hyaluronan (HA-HC). Key pro-inflammatory molecules, tumour necrosis factor alpha, interleukin-1 beta, interleukin-12, CCL3, and the co-stimulatory molecules, CD40 and CD86 were measured. Only human umbilical cord hyaluronan, bovine testes and Streptomyces hyaluronlyticus hyaluronidase stimulated macrophages and DCs, however, these reagents were found to be contaminated with endotoxin, which was not fully removed by polymyxin B treatment. In contrast, pharmaceutical grade hyaluronan and hyaluronan fragments failed to stimulate in vitro-derived or ex vivo macrophages and DCs, and did not induce leukocyte recruitment after intratracheal instillation into mouse lungs. Hence, endotoxin-free pharmaceutical grade hyaluronan does not stimulate macrophages and DCs in our inflammatory models. These results emphasize the importance of ensuring hyaluronan preparations are endotoxin free.

Indexed as

AnimalsCells, CulturedDendritic CellsHyaluronic AcidInterleukin-12Macrophage ActivationMacrophagesMiceTumor Necrosis Factor-alphaHyaluronic AcidInterleukin-12Tumor Necrosis Factor-alpha

Identifiers

PMID27869206
PMCPMC5116629
OpenAlexW2551906031

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.