Dataset Information

Atopic asthmatic patients have reduced airway inflammatory cell recruitment after inhaled endotoxin challenge compared with healthy volunteers.

ABSTRACT:

Background

Atopic asthmatic patients are reported to be more sensitive to the effects of environmental endotoxin (LPS) than healthy volunteers (HVs). It is unknown whether this sensitivity is due to dysregulated inflammatory responses after LPS exposure in atopic asthmatic patients.

Objective

We sought to test the hypothesis that atopic asthmatic patients respond differentially to inhaled LPS challenge compared with HVs.

Methods

Thirteen allergic asthmatic (AA) patients and 18 nonallergic nonasthmatic subjects (healthy volunteers [HVs]) underwent an inhalation challenge to 20,000 endotoxin units of Clinical Center Reference Endotoxin (LPS). Induced sputum and peripheral blood were obtained at baseline and 6 hours after inhaled LPS challenge. Sputum and blood samples were assayed for changes in inflammatory cell numbers and cytokine and cell-surface marker levels on monocytes and macrophages.

Results

The percentage of neutrophils in sputum (%PMN) in induced sputum similarly and significantly increased in both HVs and AA patients after inhaled LPS challenge. However, the absolute numbers of leukocytes and PMNs recruited to the airways were significantly lower in AA patients compared with those seen in HVs with inhaled LPS challenge. Sputum levels of IL-6 and TNF-? were significantly increased in both cohorts, but levels of IL-1? and IL-18 were only significantly increased in the HV group. Cell-surface expression of Toll-like receptors 4 and 2 were significantly enhanced only in the HV group.

Conclusions

The airway inflammatory response to inhaled LPS challenge is blunted in AA patients compared with that seen in HVs and accompanied by reductions in airway neutrophilia and inflammasome-dependent cytokine production. These factors might contribute to increased susceptibility to airway microbial infection or colonization in AA patients.

SUBMITTER: Hernandez ML

PROVIDER: S-EPMC3652253 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Publications

Atopic asthmatic patients have reduced airway inflammatory cell recruitment after inhaled endotoxin challenge compared with healthy volunteers.

Hernandez Michelle L ML Herbst Margaret M Lay John C JC Alexis Neil E NE Brickey Willie June WJ Ting Jenny P Y JP Zhou Haibo H Peden David B DB

The Journal of allergy and clinical immunology 20120704 4

<h4>Background</h4>Atopic asthmatic patients are reported to be more sensitive to the effects of environmental endotoxin (LPS) than healthy volunteers (HVs). It is unknown whether this sensitivity is due to dysregulated inflammatory responses after LPS exposure in atopic asthmatic patients.<h4>Objective</h4>We sought to test the hypothesis that atopic asthmatic patients respond differentially to inhaled LPS challenge compared with HVs.<h4>Methods</h4>Thirteen allergic asthmatic (AA) patients and ...[more]

PMID: 22770265

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Project description:BackgroundAllergic inflammation is commonly observed in a number of conditions that are associated with atopy including asthma, eczema and rhinitis. However, the genetic, environmental or epigenetic factors involved in these conditions are likely to be different. Epigenetic modifications, such as DNA methylation, can be influenced by the environment and result in changes to gene expression.ObjectivesTo characterize the DNA methylation pattern of airway epithelial cells (AECs) compared to peripheral blood mononuclear cells (PBMCs) and to discern differences in methylation within each cell type amongst healthy, atopic and asthmatic subjects.MethodsPBMCs and AECs from bronchial brushings were obtained from children undergoing elective surgery for non-respiratory conditions. The children were categorized as atopic, atopic asthmatic, non-atopic asthmatic or healthy controls. Extracted DNA was bisulfite treated and 1505 CpG loci across 807 genes were analyzed using the Illumina GoldenGate Methylation Cancer Panel I. Gene expression for a subset of genes was performed using RT-PCR.ResultsWe demonstrate a signature set of CpG sites that are differentially methylated in AECs as compared to PBMCs regardless of disease phenotype. Of these, 13 CpG sites were specific to healthy controls, 8 sites were only found in atopics, and 6 CpGs were unique to asthmatics. We found no differences in the methylation status of PBMCs between disease phenotypes. In AECs derived from asthmatics compared to atopics, 8 differentially methylated sites were identified including CpGs in STAT5A and CRIP1. We demonstrate STAT5A gene expression is decreased whereas CRIP1 gene expression is elevated in the AECs from asthmatic compared to both healthy and atopic subjects.DiscussionWe characterized a cell specific DNA methylation signature for AECs compared to PBMCs regardless of asthmatic or atopic status. Our data highlight the importance of understanding DNA methylation in the epithelium when studying the epithelial contribution to asthma.

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Dataset Information

Atopic asthmatic patients have reduced airway inflammatory cell recruitment after inhaled endotoxin challenge compared with healthy volunteers.

Background

Objective

Methods

Results

Conclusions

Publications

Atopic asthmatic patients have reduced airway inflammatory cell recruitment after inhaled endotoxin challenge compared with healthy volunteers.

Similar Datasets

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