Evidence map›Paper›PMID 19835594›Full record

ArticleRespiratory research2009

Differential effects of cytokines and corticosteroids on toll-like receptor 2 expression and activity in human airway epithelia.

Audra A Winder, Christine Wohlford-Lenane, Todd E Scheetz, Brie N Nardy, Lori J Manzel, Dwight C Look, Paul B McCray

Open access · goldAbstract read
In one paragraph

Article in Respiratory research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.2field-weighted citation impact, top 20% 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

14 citing papers in PubMed, 35 citations in OpenAlex.

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  13. Mallory-Denk body pathogenesis revisited.World journal of hepatology · 2010
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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.

Audra A WinderDepartment of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, USA. audra.winder@marshfieldclinic.org
Christine Wohlford-Lenane
Todd E Scheetz
Brie N Nardy
Lori J Manzel
Dwight C Look
Paul B McCray
University of Iowa · US

Funding

Vector Core-Core 2P30DK054759 · NIDDK · UNIVERSITY OF IOWA · PI Amy Leanne Ryan · 1998 to 2026
$30.5M
Xylitol Enhancement of Bacterial Killing by AirwayP50HL061234 · NHLBI · UNIVERSITY OF IOWA · PI ZABNER, JOSEPH · 1998 to 2007
$13.6M
RESEARCH TRAINING IN INFECTIOUS DISEASEST32AI007343 · NIAID · UNIVERSITY OF IOWA · PI STAPLETON, JACK T. · 1988 to 2024
$5.0M
Induction of COPD Exacerbation by Haemophilus influenzaeR01HL082505 · NHLBI · UNIVERSITY OF IOWA · PI LOOK, DWIGHT C · 2005 to 2009
$1.6M
RSV Inhibition of Interferon-Dependent Airway ImmunityR01HL075559 · NHLBI · UNIVERSITY OF IOWA · PI LOOK, DWIGHT C · 2004 to 2007
$1.2M
VIRAL RESPIRATORY PATHOGENS RESEARCH UNIT /VRPRU/-266030040-266030040N01AI030040 · NIAID · UNIVERSITY OF IOWA · PI APICELLA, MICHAEL A. · 2003 to 2006
–
NHLBI NIH HHS HL-075559NHLBI NIH HHS HL-082505NHLBI NIH HHS P50 HL-61234NIAID NIH HHS N01 AI-30040NIAID NIH HHS T32AI007343NIDDK NIH HHS P30 DK054759NIDDK NIH HHS P30 DK-54759
6 · The paper itself

Abstract

backgroundThe recognition of microbial molecular patterns via toll-like receptors (TLRs) is critical for mucosal defenses.

methodsUsing well-differentiated primary cultures of human airway epithelia, we investigated the effects of exposure of the cells to cytokines (TNF-alpha and IFN-gamma) and dexamethasone (dex) on responsiveness to the TLR2/TLR1 ligand Pam3CSK4. Production of IL-8, CCL20, and airway surface liquid antimicrobial activity were used as endpoints.

resultsMicroarray expression profiling in human airway epithelia revealed that first response cytokines markedly induced TLR2 expression. Real-time PCR confirmed that cytokines (TNF-alpha and IFN-gamma), dexamethasone (dex), or cytokines + dex increased TLR2 mRNA abundance. A synergistic increase was seen with cytokines + dex. To assess TLR2 function, epithelia pre-treated with cytokines +/- dex were exposed to the TLR2/TLR1 ligand Pam3CSK4 for 24 hours. While cells pre-treated with cytokines alone exhibited significantly enhanced IL-8 and CCL20 secretion following Pam3CSK4, mean IL-8 and CCL20 release decreased in Pam3CSK4 stimulated cells following cytokines + dex pre-treatment. This marked increase in inflammatory gene expression seen after treatment with cytokines followed by the TLR2 ligand did not correlate well with NF-kappaB, Stat1, or p38 MAP kinase pathway activation. Cytokines also enhanced TLR2 agonist-induced beta-defensin 2 mRNA expression and increased the antimicrobial activity of airway surface liquid. Dex blocked these effects.

conclusionWhile dex treatment enhanced TLR2 expression, co-administration of dex with cytokines inhibited airway epithelial cell responsiveness to TLR2/TLR1 ligand over cytokines alone. Enhanced functional TLR2 expression following exposure to TNF-alpha and IFN-gamma may serve as a dynamic means to amplify epithelial innate immune responses during infectious or inflammatory pulmonary diseases.

Indexed as

Adrenal Cortex HormonesCells, CulturedChemokine CCL20CytokinesDexamethasoneEpithelial CellsEscherichia coliGene Expression ProfilingHumansImmunity, InnateInflammation MediatorsInterferon-gammaInterleukin-1betaInterleukin-8LigandsLipopeptidesAdrenal Cortex HormonesCCL20 protein, humanChemokine CCL20CXCL8 protein, humanCytokinesDexamethasoneInflammation MediatorsInterferon-gammaInterleukin-1betaInterleukin-8LigandsLipopeptidesPam(3)CSK(4) peptideRecombinant ProteinsRNA, MessengerTLR2 protein, humanToll-Like Receptor 2Tumor Necrosis Factor-alpha

Identifiers

PMID19835594
PMCPMC2772856
OpenAlexW2142866603

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.