title: Allergic environment enhances airway epithelial pro-inflammatory responses to rhinovirus infection.
abstract: Airway epithelial cells (AEC) exhibit a pro-inflammatory phenotype in patients with allergic asthma. We examined the effect of an allergic cytokine environment on the response of AEC to rhinovirus (RV), the most common trigger of acute exacerbations of asthma. Calu-3 cells, a well-differentiated human AEC line, were cultured with or without the T-helper type 2 cytokines interleukin (IL)-4 and IL-13, then stimulated with a toll-like receptor (TLR) 3 agonist (poly I:C, dsRNA) or a TLR7 agonist (imiquimod), or infected with RV 16. Expression of pro-inflammatory and antiviral mediators, and of viral pattern-recognition molecules, was assessed using nCounter assays, quantitative real-time PCR (qRT-PCR) and protein immunoassays. Both dsRNA and imiquimod stimulated expression of mRNA forIL6 and IL8whereas expression of several chemokines and antiviral response genes was induced only by dsRNA. Conversely, expression of other cytokines and growth factors was induced only by imiquimod. RV infection not only stimulated expression of the inflammation-related genes induced by dsRNA, but also of complement factor B and the novel pro-inflammatory cytokine IL-32. In the T helper type 2 (Th2) cytokine environment, several mediators exhibited significantly enhanced expression, whereas expression of interferons was either unchanged or enhanced. The allergic environment also increased expression of pattern-recognition receptors and of intercellular adhesion molecule 1, the cell surface receptor for RV. We conclude that Th2 cytokines promote increased production of pro-inflammatory mediators by AEC following infection with RV. Increased viral entry or enhanced signalling via pattern-recognition receptors could also contribute to the exaggerated inflammatory response to RV observed in allergic asthmatics.
authors.affiliation: Department of Pathology, School of Medical Sciences, UNSW Sydney, NSW 2052, Australia.
authors.forename: Cristan
authors.initials: C
authors.lastname: Herbert
authors.affiliation: Department of Pathology, School of Medical Sciences, UNSW Sydney, NSW 2052, Australia.
authors.forename: Kimchi
authors.initials: K
authors.lastname: Do
authors.affiliation: Department of Pathology, School of Medical Sciences, UNSW Sydney, NSW 2052, Australia.
authors.forename: Vincent
authors.initials: V
authors.lastname: Chiu
authors.affiliation: Department of Pathology, School of Medical Sciences, UNSW Sydney, NSW 2052, Australia.
authors.forename: Linda
authors.initials: L
authors.lastname: Garthwaite
authors.affiliation: Department of Pathology, School of Medical Sciences, UNSW Sydney, NSW 2052, Australia.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Respiratory Cellular and Molecular Biology, Woolcock Institute of Medical Research, University of Sydney, Sydney, NSW 2037, Australia.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Young
authors.affiliation: Respiratory Cellular and Molecular Biology, Woolcock Institute of Medical Research, University of Sydney, Sydney, NSW 2037, Australia.
authors.forename: Daniela
authors.initials: D
authors.lastname: Traini
authors.affiliation: Department of Pathology, School of Medical Sciences, UNSW Sydney, NSW 2052, Australia r.kumar@unsw.edu.au.
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Kumar
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D000077271:Imiquimod; D018836:Inflammation Mediators / Q000378:metabolism*; D007369:Interferon Inducers / Q000494:pharmacology; D010850:Picornaviridae Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011070:Poly I-C / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020545:Respiratory Mucosa / Q000378:metabolism / Q000821:virology*; D012229:Rhinovirus; D018418:Th2 Cells / Q000276:immunology; D051196:Toll-Like Receptor 3 / Q000819:agonists; D051199:Toll-Like Receptor 7 / Q000819:agonists
chemical_list: D000634:Aminoquinolines; D016207:Cytokines; D018836:Inflammation Mediators; D007369:Interferon Inducers; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; C495344:TLR3 protein, human; C495348:TLR7 protein, human; D051196:Toll-Like Receptor 3; D051199:Toll-Like Receptor 7; D011070:Poly I-C; D000077271:Imiquimod
keywords: allergic asthma; exacerbations; interleukin-32; pattern-recognition receptors; rhinovirus