Evidence map›Paper›PMID 26208141›Full record

ArticleAlcoholism, clinical and experimental research2015

TLR2 and TLR4 Expression and Inflammatory Cytokines are Altered in the Airway Epithelium of Those with Alcohol Use Disorders.

Kristina L Bailey, Debra J Romberger, Dawn M Katafiasz, Art J Heires, Joseph H Sisson, Todd A Wyatt, Ellen L Burnham

Open access · greenAbstract read
In one paragraph

Article in Alcoholism, clinical and experimental research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 19% 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, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.

  1. Pooled it
  2. Myeloid TLR2 signaling amplifies immunopathology in influenza-infected murine neonates.American journal of respiratory cell and molecular biology · 2026
    Article
  3. Article
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  8. ABCF1 Regulates dsDNA-induced Immune Responses in Human Airway Epithelial Cells.Frontiers in cellular and infection microbiology · 2020
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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 3 institutions in 1 country.

Kristina L BaileyInternal Medicine, Division of Pulmonary, Critical Care, Sleep and Allergy, University of Nebraska Medical Center, Omaha, Nebraska.
Debra J RombergerInternal Medicine, Division of Pulmonary, Critical Care, Sleep and Allergy, University of Nebraska Medical Center, Omaha, Nebraska.
Dawn M KatafiaszInternal Medicine, Division of Pulmonary, Critical Care, Sleep and Allergy, University of Nebraska Medical Center, Omaha, Nebraska.
Art J HeiresInternal Medicine, Division of Pulmonary, Critical Care, Sleep and Allergy, University of Nebraska Medical Center, Omaha, Nebraska.
Joseph H SissonInternal Medicine, Division of Pulmonary, Critical Care, Sleep and Allergy, University of Nebraska Medical Center, Omaha, Nebraska.
Todd A WyattInternal Medicine, Division of Pulmonary, Critical Care, Sleep and Allergy, University of Nebraska Medical Center, Omaha, Nebraska.
Ellen L BurnhamUniversity of Colorado School of Medicine, Denver, Colorado.
University of Nebraska Medical Center · USUniversity of Colorado Denver · USVA Nebraska Western Iowa Health Care System · US

Funding

Colorado Clinical and Translational Sciences InstituteUL1TR001082 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2013 to 2017
$48.0M
Supplement: CoPARC: Colorado Pulmonary Alcohol Research CollaborativeR24AA019661 · NIAAA · UNIVERSITY OF COLORADO DENVER · PI ELLEN L BURNHAM · 2011 to 2026
$8.5M
ETHANOL MEDIATED CILIA MOTILITY DYSFUNCTIONR01AA008769 · NIAAA · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI SISSON, JOSEPH H · 1996 to 2016
$4.4M
Biphasic alcohol regulation of TLR2 in airway epitheliumK08AA019503 · NIAAA · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BAILEY, KRISTINA L · 2010 to 2014
$944k
NCATS NIH HHS UL1 TR001082NIAAA NIH HHS K08 AA019503NIAAA NIH HHS K08AA019503NIAAA NIH HHS R01 AA008769NIAAA NIH HHS R01AA008769NIAAA NIH HHS R24 AA019661NIAAA NIH HHS R24AA019661NIOSH CDC HHS U54 OH010162
6 · The paper itself

Abstract

backgroundThe lung has a highly regulated system of innate immunity to protect itself from inhaled microbes and toxins. The first line of defense is mucociliary clearance, but if invaders overcome this, inflammatory pathways are activated. Toll-like receptors (TLRs) are expressed on the airway epithelium. Their signaling initiates the inflammatory cascade and leads to production of inflammatory cytokines such as interleukin (IL)-6 and IL-8. We hypothesized that airway epithelial insults, including heavy alcohol intake or smoking, would alter the expression of TLRs on the airway epithelium.

methodsBronchoscopy with bronchoalveolar lavage and brushings of the airway epithelium was performed in otherwise healthy subjects who had normal chest radiographs and spirometry. A history of alcohol use disorders (AUDs) was ascertained using the Alcohol Use Disorders Identification Test (AUDIT), and a history of cigarette smoking was also obtained. Age, gender, and nutritional status in all groups were similar. We used real-time polymerase chain reaction (PCR) to quantitate TLR1 to 9 and enzyme-linked immune assay to measure tumor necrosis factor-α, IL-6, and IL-8.

resultsAirway brushings were obtained from 26 nonsmoking/non-AUD subjects, 28 smoking/non-AUD subjects, 36 smoking/AUD subjects, and 17 nonsmoking/AUD subjects. We found that TLR2 is up-regulated in AUD subjects, compared to nonsmoking/non-AUD subjects, and correlated with their AUDIT scores. We also measured a decrease in TLR4 expression in AUD subjects that correlated with AUDIT score. IL-6 and IL-8 were also increased in bronchial washings from AUD subjects.

conclusionsWe have previously demonstrated in normal human bronchial epithelial cells that in vitro alcohol exposure up-regulates TLR2 through a NO/cGMP/PKG-dependent pathway, resulting in up-regulation of inflammatory cytokine production after Gram-positive bacterial product stimulation. Our current translational study confirms that TLR2 is also up-regulated in humans with AUDs.

Indexed as

AdultAlcohol-Related DisordersCells, CulturedCohort StudiesCytokinesFemaleGene Expression RegulationHumansInflammation MediatorsMaleMiddle AgedRespiratory MucosaToll-Like Receptor 2Toll-Like Receptor 4CytokinesInflammation MediatorsTLR2 protein, humanTLR4 protein, humanToll-Like Receptor 2Toll-Like Receptor 4Airway EpitheliumCytokinesHumanToll-Like Receptors

Identifiers

PMID26208141
PMCPMC4843766
OpenAlexW1870551604

What OpenQuestion holds

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Registered trials

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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.