title: The clinical and environmental determinants of airway transcriptional profiles in allergic asthma.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA. ivana.yang@ucdenver.edu
authors.forename: Ivana V
authors.initials: IV
authors.lastname: Yang
authors.forename: John
authors.initials: J
authors.lastname: Tomfohr
authors.forename: Jaspal
authors.initials: J
authors.lastname: Singh
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Foss
authors.forename: Harvey E
authors.initials: HE
authors.lastname: Marshall
authors.forename: Loretta G
authors.initials: LG
authors.lastname: Que
authors.forename: Erin
authors.initials: E
authors.lastname: McElvania-Tekippe
authors.forename: Sarita
authors.initials: S
authors.lastname: Florence
authors.forename: John S
authors.initials: JS
authors.lastname: Sundy
authors.forename: David A
authors.initials: DA
authors.lastname: Schwartz
mesh_terms: D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001249:Asthma / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004781:Environmental Exposure / Q000009:adverse effects*; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D006967:Hypersensitivity / Q000150:complications* / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate; D007073:Immunoglobulin E / Q000276:immunology; D008297:Male; D012313:RNA / Q000235:genetics; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: D000888:Antibodies, Anti-Idiotypic; D016207:Cytokines; D007073:Immunoglobulin E; D012313:RNA