Double-stranded RNA induces disproportionate expression of thymic stromal lymphopoietin versus interferon-β in bronchial epithelial cells from donors with asthma

• Published in: Thorax Vol. 65; no. 7; pp. 626 - 632
• Main Authors: Uller, Lena, Leino, Marina, Bedke, Nicole, Sammut, David, Green, Ben, Lau, Laurie, Howarth, Peter H, Holgate, Stephen T, Davies, Donna E
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Thoracic Society 01.07.2010; BMJ Publishing Group
• Subjects: Adult; airway epithelium; asthma; Asthma - immunology; asthma mechanisms; Biological and medical sciences; Bronchi - immunology; Bronchoscopy - methods; Cardiology. Vascular system; Cells, Cultured; Chronic obstructive pulmonary disease, asthma; Cytokines - biosynthesis; Cytokines - genetics; Dose-Response Relationship, Immunologic; epithelial cells; Epithelial Cells - immunology; exacerbation; Female; Gene Expression Regulation - drug effects; Humans; Immunity, Innate; innate immunity; Interferon; Interferon-beta - biosynthesis; Interleukin-8 - biosynthesis; Male; Medical sciences; Middle Aged; Pneumology; Protein Kinase Inhibitors - pharmacology; Respiratory Mucosa - immunology; rhinovirus; RNA, Double-Stranded - immunology; RNA, Messenger - genetics; Thymic Stromal Lymphopoietin; Toll-Like Receptor 3 - antagonists & inhibitors; TSLP; Young Adult; Suboptimal donor; Human; Lung disease; Double stranded RNA; Thymus gland; Respiratory disease; Cytokine; Bronchus; Gene expression; Asthma; Bronchus disease; Anesthesia; Antiviral; Epithelial cell; Interferon; Obstructive pulmonary disease; Circulatory system; β Cell; Cardiology; Comparative study
• ISSN: 0040-6376; 1468-3296; 1468-3296
• DOI: 10.1136/thx.2009.125930

BackgroundThymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that strongly activates dendritic cells and can initiate allergic inflammation. Since exposure to rhinovirus or double-stranded (ds) RNA (a surrogate of viral infection) induces TSLP expression in bronchial epithelial cells (BECs), this cytokine may link innate antiviral responses and the type 2 adaptive immune response.ObjectiveAs BECs from donors with asthma have a deficient interferon (IFN) response to rhinovirus infection, a study was undertaken to test the hypothesis that their antiviral response shows a bias towards TSLP production.MethodsPrimary BECs were grown from subjects with asthma and healthy volunteers. After exposure to dsRNA, interleukin (IL)-8, IFNβ and TSLP mRNA and protein expression were measured by RT-qPCR and ELISA, respectively.ResultsdsRNA dose-dependently increased IL-8 expression in BECs with no significant difference between the groups. However, BECs from subjects with asthma expressed less IFNβ and more TSLP mRNA and protein in response to dsRNA than BECs from those without asthma (median (IQR) 57 (38–82) pg/ml vs 106 (57–214) pg/ml for IFNβ (p<0.05) and 114 (86–143) pg/ml vs 65 (32–119) pg/ml for TSLP (p<0.05) in response to 10 μg/ml dsRNA for 24 h). Induction of TSLP mRNA by dsRNA was blocked by Toll-like receptor 3 or protein kinase inhibitors or by preventing de novo protein synthesis, but not by neutralisation of type I IFN receptors.ConclusionBECs from subjects with asthma are biased towards higher TSLP and lower IFNβ production in response to dsRNA, suggesting that viral infection in asthma may lead to an altered mediator profile that biases towards a Th2 immune response.