Evidence map›Paper›PMID 26367274›Full record

Trial reportPloS one2015

Mycobacterium tuberculosis Upregulates TNF-α Expression via TLR2/ERK Signaling and Induces MMP-1 and MMP-9 Production in Human Pleural Mesothelial Cells.

Wei-Lin Chen, Joen-Rong Sheu, Ray-Jade Chen, Shih-Hsin Hsiao, Che-Jen Hsiao, Yung-Chen Chou, Chi-Li Chung, George Hsiao

Open access · goldAbstract readClinical Trial
In one paragraph

Trial report in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 8% 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

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.

  1. Pooled it
  2. Article
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  6. Article
  7. [Expression of circRNA_051778 in Lung Adenocarcinoma-Associated Malignant and Tuberculous Pleural Effusions and Its Clinical Significance].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024
    Article
  8. Review
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  10. Heliyon · 2022
    Article
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  14. FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
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  17. Review
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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

8 authors at 2 institutions in 1 country.

Wei-Lin ChenGraduate Institute of Medical Sciences and Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Joen-Rong SheuGraduate Institute of Medical Sciences and Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Ray-Jade ChenDepartment of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of General Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei, Taiwan.
Shih-Hsin HsiaoDivision of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.
Che-Jen HsiaoSchool of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Yung-Chen ChouGraduate Institute of Medical Sciences and Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Chi-Li ChungDivision of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan; School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan.
George HsiaoGraduate Institute of Medical Sciences and Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Taipei Medical University · TWTaipei Medical University Hospital · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTumor necrosis factor (TNF)-α and matrix metalloproteinases (MMPs) are elevated in pleural fluids of tuberculous pleuritis (TBP) where pleural mesothelial cells (PMCs) conduct the first-line defense against Mycobacterium tuberculosis (MTB). However, the clinical implication of TNF-α and MMPs in TBP and the response of PMCs to MTB infection remain unclear.

methodsWe measured pleural fluid levels of TNF-α and MMPs in patients with TBP (n = 18) or heart failure (n = 18) as controls. Radiological scores for initial effusion amount and residual pleural fibrosis at 6-month follow-up were assessed. In vitro human PMC experiments were performed to assess the effect of heat-killed M. tuberculosis H37Ra (MTBRa) on the expression of TNF-α and MMPs.

resultsAs compared with controls, the effusion levels of TNF-α, MMP-1 and MMP-9 were significantly higher and correlated positively with initial effusion amount in patients with TBP, while TNF-α and MMP-1, but not MMP-9, were positively associated with residual pleural fibrosis of TBP. Moreover, effusion levels of TNF-α had positive correlation with those of MMP-1 and MMP-9 in TBP. In cultured PMCs, MTBRa enhanced TLR2 and TLR4 expression, activated ERK signaling, and upregulated TNF-α mRNA and protein expression. Furthermore, knockdown of TLR2, but not TLR4, significantly inhibited ERK phosphorylation and TNF-α expression. Additionally, both MTBRa and TNF-α markedly induced MMP-1 and MMP-9 synthesis in human PMCs, and TNF-α neutralization substantially reduced the production of MMP-1, but not MMP-9, in response to MTBRa stimulation.

conclusionMTBRa activates TLR2/ERK signalings to induce TNF-α and elicit MMP-1 and MMP-9 in human PMCs, which are associated with effusion volume and pleural fibrosis and may contribute to pathogenesis of TBP. Further investigation of manipulation of TNF-α and MMP expression in pleural mesothelium may provide new insights into the mechanisms and rational treatment strategies for TBP.

Indexed as

AdultAgedAged, 80 and overCell LineEpithelial CellsFemaleHumansMaleMAP Kinase Signaling SystemMatrix Metalloproteinase 1Matrix Metalloproteinase 9Middle AgedMycobacterium tuberculosisPleuraToll-Like Receptor 2Tuberculosis, PulmonaryMatrix Metalloproteinase 1Matrix Metalloproteinase 9MMP1 protein, humanTLR2 protein, humanToll-Like Receptor 2Tumor Necrosis Factor-alpha

Identifiers

PMID26367274
PMCPMC4569295
OpenAlexW2248246836

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LicenceCC BY
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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.