TY - JOUR
T1 - The clinical and environmental determinants of airway transcriptional profiles in allergic asthma
AU - Yang, Ivana V.
AU - Tomfohr, John
AU - Singh, Jaspal
AU - Foss, Catherine M.
AU - Marshall, Harvey E.
AU - Que, Loretta G.
AU - McElvania-Tekippe, Erin
AU - Florence, Sarita
AU - Sundy, John S.
AU - Schwartz, David A.
PY - 2012/3/15
Y1 - 2012/3/15
N2 - 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 andatopyphenotype. Finally, although no consistent expression changes were observed across all subjects in response to house dustmite 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.
AB - 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 andatopyphenotype. Finally, although no consistent expression changes were observed across all subjects in response to house dustmite 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.
KW - Atopy
KW - Environmental asthma
KW - House dust mite
KW - Lipopolysaccharide
KW - Microarray
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U2 - 10.1164/rccm.201108-1503OC
DO - 10.1164/rccm.201108-1503OC
M3 - Article
C2 - 22246175
AN - SCOPUS:84858234306
SN - 1073-449X
VL - 185
SP - 620
EP - 627
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 6
ER -