Evidence map›Paper›PMID 36230982›Full record

ArticleCells2022

The Distinctive Activation of Toll-Like Receptor 4 in Human Samples with Sepsis.

Patrick Thon, Katharina Rump, Annika Knorr, Birte Dyck, Dominik Ziehe, Matthias Unterberg, Hartmuth Nowak, Lars Bergmann, Alexander Wolf, Maha Bazzi and 7 more

Open access · goldAbstract read
In one paragraph

Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.5field-weighted citation impact, top 39% 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

8 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Cells · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. AQP3 and AQP9-Contrary Players in Sepsis?International journal of molecular sciences · 2024
    Article
  8. 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

17 authors at 4 institutions in 1 country.

Patrick ThonKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, Germany.
Katharina RumpKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, Germany.ORCID 0000-0003-2220-519X
Annika KnorrKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, Germany.
Birte DyckKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, Germany.
Dominik ZieheKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, Germany.
Matthias UnterbergKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, Germany.
Hartmuth NowakKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, Germany.ORCID 0000-0002-6509-1463
Lars BergmannKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, Germany.ORCID 0000-0002-8603-8549
Alexander WolfKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, Germany.
Maha BazziKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, Germany.
Jennifer OrlowskiKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, Germany.
Marcus PetersMolekulare Immunologie, Ruhr-University Bochum, 44780 Bochum, Germany.ORCID 0000-0003-1850-2845
Alexander ZarbockKlinik für Anästhesiologie, Operative Intensivmedizin und Schmerztherapie, Universitätsklinikum Münster, 48149 Münster, Germany.
Thorsten BrennerDepartment of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.
Michael AdamzikKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, Germany.
Tim RahmelKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, Germany.ORCID 0000-0002-7039-6288
Björn KoosKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, Germany.ORCID 0000-0002-0544-4124
Universitätsklinikum Knappschaftskrankenhaus Bochum · DERuhr University Bochum · DEUniversity Hospital Münster · DEUniversity of Duisburg-Essen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Clinical success of Toll-Like receptor-4 (TLR-4) antagonists in sepsis therapy has thus far been lacking. As inhibition of a receptor can only be useful if the receptor is active, stratification of patients with active TLR-4 would be desirable. Our aim was to establish an assay to quantify phosphorylated TLR-4 using the proximity ligation assay (PLA). HEK293 TLR4/MD2/CD14 as well as THP-1 cells were stimulated with LPS and the activation of TLR-4 was measured using the PLA. Furthermore, peripheral blood mononuclear cells (PBMCs) from 25 sepsis patients were used to show the feasibility of this assay in clinical material. Activation of TLR-4 in these samples was compared to the PBMCs of 11 healthy individuals. We could show a transient activation of TLR-4 in both cell lines. Five min after the LPS stimulation, the signal increased 6.7-fold in the HEK293 cells and 4.3-fold in the THP-1 cells. The assay also worked well in the PBMCs of septic patients. Phosphorylation of TLR-4 at study inclusion was 2.9 times higher in septic patients compared to healthy volunteers. To conclude, we established a diagnostic assay that is able to quantify the phosphorylation of TLR-4 in cell culture and in clinical samples of sepsis patients. This makes large-scale stratification of sepsis patients for their TLR-4 activation status possible.

Indexed as

SepsisHEK293 CellsHumansLeukocytes, MononuclearLipopolysaccharidesToll-Like Receptor 4LipopolysaccharidesTLR4 protein, humanToll-Like Receptor 4proximity ligation assaysepsisToll-Like Receptor 4

Identifiers

PMID36230982
PMCPMC9563554
OpenAlexW4297348405

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.