Evidence map›Paper›PMID 27524890›Full record

ArticleInternational journal of chronic obstructive pulmonary disease2016

An antagonist of the platelet-activating factor receptor inhibits adherence of both nontypeable Haemophilus influenzae and Streptococcus pneumoniae to cultured human bronchial epithelial cells exposed to cigarette smoke.

Shakti D Shukla, Rory L Fairbairn, David A Gell, Roger D Latham, Sukhwinder S Sohal, Eugene H Walters, Ronan F O'Toole

Open access · goldAbstract read
In one paragraph

Article in International journal of chronic obstructive pulmonary disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
5.9field-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

23 citing papers in PubMed, 40 citations in OpenAlex.

  1. Review
  2. Article
  3. Non-typeableEuropean respiratory review : an official journal of the European Respiratory Society · 2022
    Review
  4. Article
  5. Fully integrating pathophysiological insights in COPD: an updated working disease model to broaden therapeutic vision.European respiratory review : an official journal of the European Respiratory Society · 2021
    Review
  6. Article
  7. Honeysuckle (Frontiers in pharmacology · 2021
    Article
  8. Review
  9. An in vivo atlas of host-pathogen transcriptomes duringProceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  10. Review
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  12. Article
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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

7 authors at 1 institution in 1 country.

Shakti D ShuklaBreathe Well Centre, School of Medicine, Faculty of Health, University of Tasmania, Hobart, TAS, Australia.
Rory L FairbairnBreathe Well Centre, School of Medicine, Faculty of Health, University of Tasmania, Hobart, TAS, Australia.
David A GellBreathe Well Centre, School of Medicine, Faculty of Health, University of Tasmania, Hobart, TAS, Australia.
Roger D LathamBreathe Well Centre, School of Medicine, Faculty of Health, University of Tasmania, Hobart, TAS, Australia.
Sukhwinder S SohalBreathe Well Centre, School of Medicine, Faculty of Health, University of Tasmania, Hobart, TAS, Australia; School of Health Sciences, Faculty of Health, University of Tasmania, Launceston, TAS, Australia.
Eugene H WaltersBreathe Well Centre, School of Medicine, Faculty of Health, University of Tasmania, Hobart, TAS, Australia.
Ronan F O'TooleBreathe Well Centre, School of Medicine, Faculty of Health, University of Tasmania, Hobart, TAS, Australia.
University of Tasmania · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCOPD is emerging as the third largest cause of human mortality worldwide after heart disease and stroke. Tobacco smoking, the primary risk factor for the development of COPD, induces increased expression of platelet-activating factor receptor (PAFr) in the lung epithelium. Nontypeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae adhere to PAFr on the luminal surface of human respiratory tract epithelial cells.

objectiveTo investigate PAFr as a potential drug target for the prevention of infections caused by the main bacterial drivers of acute exacerbations in COPD patients, NTHi and S. pneumoniae.

methodsHuman bronchial epithelial BEAS-2B cells were exposed to cigarette smoke extract (CSE). PAFr expression levels were determined using immunocytochemistry and quantitative polymerase chain reaction. The epithelial cells were challenged with either NTHi or S. pneumoniae labeled with fluorescein isothiocyanate, and bacterial adhesion was measured using immunofluorescence. The effect of a well-evaluated antagonist of PAFr, WEB-2086, on binding of the bacterial pathogens to BEAS-2B cells was then assessed. In silico studies of the tertiary structure of PAFr and the binding pocket for PAF and its antagonist WEB-2086 were undertaken.

resultsPAFr expression by bronchial epithelial cells was upregulated by CSE, and significantly associated with increased bacterial adhesion. WEB-2086 reduced the epithelial adhesion by both NTHi and S. pneumoniae to levels observed for non-CSE-exposed cells. Furthermore, it was nontoxic toward the bronchial epithelial cells. In silico analyses identified a binding pocket for PAF/WEB-2086 in the predicted PAFr structure.

conclusionWEB-2086 represents an innovative class of candidate drugs for inhibiting PAFr-dependent lung infections caused by the main bacterial drivers of smoking-related COPD.

Indexed as

Anti-Bacterial AgentsAzepinesBacterial AdhesionBinding SitesBronchiCell LineEpithelial CellsHaemophilus InfectionsHaemophilus influenzaeHost-Pathogen InteractionsHumansMolecular Docking SimulationPlatelet Membrane GlycoproteinsPneumococcal InfectionsProtein BindingProtein ConformationAnti-Bacterial AgentsAzepinesplatelet activating factor receptorPlatelet Membrane GlycoproteinsReceptors, G-Protein-CoupledSmokeTriazolesWEB 2086airway epitheliumNTHiPAFr antagonistplatelet-activating factor receptorpneumococciWEB-2086

Identifiers

PMID27524890
PMCPMC4965220
OpenAlexW2484530403

What OpenQuestion holds

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LicenceCC BY-NC
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.