Evidence map›Paper›PMID 25303153›Full record

ArticlePloS one2014

The role of TLR2 and 4-mediated inflammatory pathways in endothelial cells exposed to high glucose.

Harshini Mudaliar, Carol Pollock, Jin Ma, Huiling Wu, Steven Chadban, Usha Panchapakesan

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

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
8.4field-weighted citation impact, top 1% 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

53 citing papers in PubMed, 103 citations in OpenAlex.

  1. Article
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  13. Macrophage pathology in hepatotoxicity.Journal of toxicologic pathology · 2023
    Review
  14. Mechanism of the antidiabetic action ofFrontiers in nutrition · 2023
    Review
  15. Article
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  17. Article
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  19. Article
  20. Article
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

6 authors at 3 institutions in 1 country.

Harshini MudaliarRenal Research Group, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
Carol PollockRenal Research Group, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
Jin MaRenal Medicine Royal Prince Alfred Hospital and Collaborative Transplant Research Group, University of Sydney, Camperdown, New South Wales, Australia.
Huiling WuRenal Medicine Royal Prince Alfred Hospital and Collaborative Transplant Research Group, University of Sydney, Camperdown, New South Wales, Australia.
Steven ChadbanRenal Medicine Royal Prince Alfred Hospital and Collaborative Transplant Research Group, University of Sydney, Camperdown, New South Wales, Australia.
Usha PanchapakesanRenal Research Group, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
Royal Prince Alfred Hospital · AUUniversity of Sydney · AURoyal North Shore Hospital · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Postprandial hyperglycemia induces inflammation and endothelial dysfunction resulting in vascular complications in patients with diabetes. Toll-like receptors (TLRs) are central to the regulation of inflammatory responses through activation of nuclear factor-kappa B (NF-ĸB). This study examined the role of TLR2 and 4 in regulating inflammation and endothelial dysfunction when exposed to fluctuating glucose concentrations. HMEC-1 cells (a human microvascular endothelial cell line) were exposed to control (5 mM), 30 mM (high), fluctuating (5/30 mM) and 11.2 mM glucose (approximate glycaemic criteria for the diagnosis of diabetes mellitus) for 72 h. Cells were assessed for TLR2, 4, high mobility group box -1 (HMGB1), NF-ĸB, monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Fluctuating glucose concentrations maximally upregulated TLR4 but not TLR2 expression with increased NF-ĸB activation, IL-8 and ICAM-1 expression. HMGB1 was increased in the supernatants of cells exposed to 30 mM and 11.2 mM glucose compared to control. The addition of recombinant HMGB1 induced NF-ĸB activation and synthesis of proinflammatory cytokines and chemokines, which were prevented by TLR2 or 4 signalling inhibition. An additive effect when both TLR2 and 4 signalling pathways were inhibited was observed. However, only inhibition of TLR4 signalling suppressed the synthesis of MCP-1, IL-8 and ICAM-1. In vivo, streptozotocin-induced diabetic mice exhibited an increase in glomerular ICAM-1 which was not evident in TLR2(-/-) or TLR4(-/-) diabetic mice. Collectively, our results suggest that targeting the signalling pathway of TLR2 and 4 may be of therapeutic benefit in attenuating vascular inflammation in diabetic microangiopathy.

Indexed as

AnimalsCell LineDiabetes Mellitus, ExperimentalEndothelial CellsGene DeletionGlucoseHumansInflammationIntercellular Adhesion Molecule-1Mice, Inbred BALB CSignal TransductionToll-Like Receptor 2Toll-Like Receptor 4GlucoseIntercellular Adhesion Molecule-1Toll-Like Receptor 2Toll-Like Receptor 4

Identifiers

PMID25303153
PMCPMC4193767
OpenAlexW2090169194

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.