Evidence map›Paper›PMID 27760316›Full record

ArticleCell reports2016

HMGB1 Activates Proinflammatory Signaling via TLR5 Leading to Allodynia.

Nabanita Das, Varun Dewan, Peter M Grace, Robin J Gunn, Ryo Tamura, Netanel Tzarum, Linda R Watkins, Ian A Wilson, Hang Yin

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed
6.2field-weighted citation impact, top 3% 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

82 citing papers in PubMed, 157 citations in OpenAlex.

  1. Review
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  13. Pathology of pain and its implications for therapeutic interventions.Signal transduction and targeted therapy · 2024
    Review
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  15. Article
  16. Article
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  18. Review
  19. Article
  20. Toll-like Receptors and Thrombopoiesis.International journal of molecular sciences · 2023
    Review

22 more citing papers are in PubMed but not listed here.

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

9 authors at 2 institutions in 1 country.

Nabanita DasDepartment of Chemistry and Biochemistry and the BioFrontiers Institute, University of Colorado, Boulder, CO 80309, USA.
Varun DewanDepartment of Chemistry and Biochemistry and the BioFrontiers Institute, University of Colorado, Boulder, CO 80309, USA.
Peter M GraceDepartment of Psychology and Neuroscience and the Center for Neuroscience, University of Colorado, Boulder, CO 80309, USA.
Robin J GunnDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Ryo TamuraDepartment of Chemistry and Biochemistry and the BioFrontiers Institute, University of Colorado, Boulder, CO 80309, USA.
Netanel TzarumDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Linda R WatkinsDepartment of Psychology and Neuroscience and the Center for Neuroscience, University of Colorado, Boulder, CO 80309, USA.
Ian A WilsonDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA; Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Hang YinDepartment of Chemistry and Biochemistry and the BioFrontiers Institute, University of Colorado, Boulder, CO 80309, USA. Electronic address: hubert.yin@colorado.edu.
University of Colorado Boulder · USScripps Research Institute · US

Funding

Structural Basis of T Cell Receptor RecognitionR37AI042266 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI WILSON, IAN A · 2003 to 2012
$5.8M
Structural basis of TLR and NLR recognition and signalingR01AI042266 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI WILSON, IAN A · 1998 to 2017
$3.7M
Exogenous Chemical Probes of TLR-Mediated NeuroinflammationR01GM101279 · NIGMS · UNIVERSITY OF COLORADO · PI YIN, HANG HUBERT · 2013 to 2017
$1.4M
NIAID NIH HHS R01 AI042266NIAID NIH HHS R37 AI042266NIGMS NIH HHS R01 GM101279
6 · The paper itself

Abstract

Infectious and sterile inflammatory diseases are correlated with increased levels of high mobility group box 1 (HMGB1) in tissues and serum. Extracellular HMGB1 is known to activate Toll-like receptors (TLRs) 2 and 4 and RAGE (receptor for advanced glycation endproducts) in inflammatory conditions. Here, we find that TLR5 is also an HMGB1 receptor that was previously overlooked due to lack of functional expression in the cell lines usually used for studying TLR signaling. HMGB1 binding to TLR5 initiates the activation of NF-κB signaling pathway in a MyD88-dependent manner, resulting in proinflammatory cytokine production and pain enhancement in vivo. Biophysical and in vitro results highlight an essential role for the C-terminal tail region of HMGB1 in facilitating interactions with TLR5. These results suggest that HMGB1-modulated TLR5 signaling is responsible for pain hypersensitivity.

Indexed as

Signal TransductionAmino Acid SequenceAnimalsBinding SitesCytokinesHEK293 CellsHMGB1 ProteinHumansHyperalgesiaInflammationJurkat CellsMaleMiceNF-kappa BNitric OxideProtein BindingCytokinesHMGB1 ProteinNF-kappa BNitric OxideToll-Like Receptor 5cytokinesHMGB1inflammationpainToll-like receptors

Identifiers

PMID27760316
PMCPMC5087801
OpenAlexW2534617315

What OpenQuestion holds

Textmetadata
LicenceTDM
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.