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J Allergy Clin Immunol. 2012 Feb;129(2):388-96, 396.e1-8. doi: 10.1016/j.jaci.2011.11.037. Epub 2011 Dec 28.

Airway TGF-β1 and oxidant stress in children with severe asthma: association with airflow limitation.

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  • 1Department of Pediatrics, Emory University, Atlanta, GA, USA.

Abstract

BACKGROUND:

TGF-β1 is thought to play a role in airway remodeling in asthmatic subjects. TGF-β1 expression might be mediated by an excessive burden of reactive oxygen species and oxidant stress.

OBJECTIVE:

Given the profound airway oxidant stress we have previously observed in children with severe asthma, we sought to (1) quantify TGF-β1 protein and mRNA gene expression in the airways of children with mild-to-moderate and severe atopic asthma and (2) determine the relationship of airway TGF-β1 concentrations to oxidant burden (ie, lipid peroxidation), T(H)2-mediated eosinophilic inflammation, and airflow limitation.

METHODS:

Bronchoalveolar lavage fluid was collected from 68 atopic children with asthma (severe asthma, n = 28) and 12 atopic adult control subjects. Airway TGF-β1 expression and activation were assessed in relation to airway IL-13, 8-isoprostane, and malondialdehyde concentrations. The relationship of airway TGF-β1 expression to airflow limitation in children with asthma was also assessed.

RESULTS:

Children with severe asthma had higher total airway concentrations of TGF-β1 that were associated with increased protein and mRNA expression of TGF-β1 in airway macrophages and an increase in concentrations of the lipid peroxidation biomarkers 8-isoprostanes and malondialdehyde. TGF-β1 activation was also greater in children with severe asthma and was associated with higher airway 8-isoprostane, malondialdehyde, and IL-13 concentrations. Total airway TGF-β1 concentrations were further associated with airflow limitation.

CONCLUSIONS:

Children with severe asthma have increased airway TGF-β1 expression and activation associated with an increased airway oxidant burden. Oxidant stress might mediate the effects of TGF-β1 and promote airway remodeling in children with severe asthma.

Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

PMID:
22206775
[PubMed - indexed for MEDLINE]
PMCID:
PMC3268912
Free PMC Article

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