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The clinical and environmental determinants of airway transcriptional profiles in allergic asthma.

Abstract

RATIONALE
Gene expression profiling of airway epithelial and inflammatory cells can be used to identify genes involved in environmental asthma.
METHODS
Airway epithelia and inflammatory cells were obtained via bronchial brush and bronchoalveolar lavage (BAL) from 39 subjects comprising three phenotypic groups (nonatopic nonasthmatic, atopic nonasthmatic, and atopic asthmatic) 4 hours after instillation of LPS, house dust mite antigen, and saline in three distinct subsegmental bronchi. RNA transcript levels were assessed using whole genome microarrays.
MEASUREMENTS AND MAIN RESULTS
Baseline (saline exposure) differences in gene expression were related to airflow obstruction in epithelial cells (C3, ALOX5AP, CCL18, and others), and to serum IgE (innate immune genes and focal adhesion pathway) and allergic-asthmatic phenotype (complement genes, histone deacetylases, and GATA1 transcription factor) in inflammatory cells. LPS stimulation resulted in pronounced transcriptional response across all subjects in both airway epithelia and BAL cells, with strong association to nuclear factor-κB and IFN-inducible genes as well as signatures of other transcription factors (NRF2, C/EBP, and E2F1) and histone proteins. No distinct transcriptional profile to LPS was observed in the asthma and atopy phenotype. Finally, although no consistent expression changes were observed across all subjects in response to house dust mite antigen stimulation, we observed subtle differences in gene expression (e.g., GATA1 and GATA2) in BAL cells related to the asthma and atopy phenotype.
CONCLUSIONS
Our results indicate that among individuals with allergic asthma, transcriptional changes in airway epithelia and inflammatory cells are influenced by phenotype as well as environmental exposures.

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  • Authors

    Yang IV, Tomfohr J, Singh J, Foss CM, Marshall HE, Que LG, McElvania-Tekippe E, Florence S, Sundy JS, Schwartz DA

    Source

    American journal of respiratory and critical care medicine 185:6 2012 Mar 15 pg 620-7

    MeSH

    Adult
    Antibodies, Anti-Idiotypic
    Asthma
    Bronchoalveolar Lavage Fluid
    Cytokines
    Environmental Exposure
    Epithelial Cells
    Female
    Follow-Up Studies
    Gene Expression
    Humans
    Hypersensitivity
    Immunity, Innate
    Immunoglobulin E
    Male
    RNA
    Respiratory Mucosa
    Young Adult

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, N.I.H., Intramural

    Language

    eng

    PubMed ID

    22246175