Abstract
BackgroundRhinovirus infections are the most common cause of asthma exacerbations. The complex responses by airway epithelium to rhinovirus can be captured by gene expression profiling. We hypothesized that: a) upper and lower airway epithelium exhibit differential responses to double-stranded RNA (dsRNA), and b) that this is modulated by the presence of asthma and allergic rhinitis.ObjectivesIdentification of dsRNA-induced gene expression profiles of primary nasal and bronchial epithelial cells from the same individuals and examining the impact of allergic rhinitis with and without concomitant allergic asthma on expression profiles.MethodsThis study had a cross-sectional design including 18 subjects: 6 patients with allergic asthma with concomitant rhinitis, 6 patients with allergic rhinitis, and 6 healthy controls. Comparing 6 subjects per group, the estimated false discovery rate was approximately 5%. RNA was extracted from isolated and cultured primary epithelial cells from nasal biopsies and bronchial brushings stimulated with dsRNA (poly(I:C)), and analyzed by microarray (Affymetrix U133+ PM Genechip Array). Data were analysed using R and the Bioconductor Limma package. Overrepresentation of gene ontology groups were captured by GeneSpring GX12.ResultsIn total, 17 subjects completed the study successfully (6 allergic asthma with rhinitis, 5 allergic rhinitis, 6 healthy controls). dsRNA-stimulated upper and lower airway epithelium from asthma patients demonstrated significantly fewer induced genes, exhibiting reduced down-regulation of mitochondrial genes. The majority of genes related to viral responses appeared to be similarly induced in upper and lower airways in all groups. However, the induction of several interferon-related genes (IRF3, IFNAR1, IFNB1, IFNGR1, IL28B) was impaired in patients with asthma.ConclusionsdsRNA differentially changes transcriptional profiles of primary nasal and bronchial epithelial cells from patients with allergic rhinitis with or without asthma and controls. Our data suggest that respiratory viruses affect mitochondrial genes, and we identified disease-specific genes that provide potential targets for drug development.
Highlights
Rhinovirus infections are the most common cause of asthma exacerbations
Our data suggest that respiratory viruses affect mitochondrial genes, and we identified disease-specific genes that provide potential targets for drug development
In conclusion, we demonstrated that there are differences between rhinitis patients with and without asthma in the epithelial expression of Double-stranded RNA (dsRNA)-induced genes, which are related to interferons and mitochondrial function
Summary
Rhinovirus infections are the most common cause of asthma exacerbations. The complex responses by airway epithelium to rhinovirus can be captured by gene expression profiling. Viral respiratory tract infections are the most common cause of asthma exacerbations [1], with rhinovirus (RV) being the most prominent virus involved. Patients with asthma are not at increased risk of a viral infection as compared to healthy controls, but in case of an upper respiratory infection they are more prone to develop a lower respiratory tract infection with more severe symptoms [2]. This suggests that host characteristics are contributing to the clinical responses to virus infections in asthma. In order to develop effective interventions for the prophylaxis and treatment of virus-induced exacerbations in asthma, it is mandatory to map the responses of both upper and lower airways to respiratory viruses in patients with asthma and/or rhinitis
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