title: Impaired airway epithelial cell responses from children with asthma to rhinoviral infection.
abstract: The airway epithelium forms an effective immune and physical barrier that is essential for protecting the lung from potentially harmful inhaled stimuli including viruses. Human rhinovirus (HRV) infection is a known trigger of asthma exacerbations, although the mechanism by which this occurs is not fully understood.
  
  
  
  To explore the relationship between apoptotic, innate immune and inflammatory responses to HRV infection in airway epithelial cells (AECs) obtained from children with asthma and non-asthmatic controls. In addition, to test the hypothesis that aberrant repair of epithelium from asthmatics is further dysregulated by HRV infection.
  
  
  
  Airway epithelial brushings were obtained from 39 asthmatic and 36 non-asthmatic children. Primary cultures were established and exposed to HRV1b and HRV14. Virus receptor number, virus replication and progeny release were determined. Epithelial cell apoptosis, IFN-β production, inflammatory cytokine release and epithelial wound repair and proliferation were also measured.
  
  
  
  Virus proliferation and release was greater in airway epithelial cells from asthmatics but this was not related to the number of virus receptors. In epithelial cells from asthmatic children, virus infection dampened apoptosis, reduced IFN-β production and increased inflammatory cytokine production. HRV1b infection also inhibited wound repair capacity of epithelial cells isolated from non-asthmatic children and exaggerated the defective repair response seen in epithelial cells from asthmatics. Addition of IFN-β restored apoptosis, suppressed virus replication and improved repair of airway epithelial cells from asthmatics but did not reduce inflammatory cytokine production.
  
  
  
  Collectively, HRV infection delays repair and inhibits apoptotic processes in epithelial cells from non-asthmatic and asthmatic children. The delayed repair is further exaggerated in cells from asthmatic children and is only partially reversed by exogenous IFN-β.
authors.affiliation: Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, WA, Australia. Anthony.Kicic@telethonkids.org.au.|School of Paediatrics and Child Health, The University of Western Australia, Nedlands, WA, Australia. Anthony.Kicic@telethonkids.org.au.|Telethon Kids Institute, Centre for Health Research, The University of Western Australia, Nedlands, WA, Australia. Anthony.Kicic@telethonkids.org.au.|Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, The University of Western Australia and Harry Perkins Institute of Medical Research, Nedlands, WA, Australia. Anthony.Kicic@telethonkids.org.au.
authors.forename: A
authors.initials: A
authors.lastname: Kicic
authors.affiliation: School of Paediatrics and Child Health, The University of Western Australia, Nedlands, WA, Australia.|Telethon Kids Institute, Centre for Health Research, The University of Western Australia, Nedlands, WA, Australia.
authors.forename: P T
authors.initials: PT
authors.lastname: Stevens
authors.affiliation: Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, WA, Australia.|Telethon Kids Institute, Centre for Health Research, The University of Western Australia, Nedlands, WA, Australia.
authors.forename: E N
authors.initials: EN
authors.lastname: Sutanto
authors.affiliation: Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, WA, Australia.|Telethon Kids Institute, Centre for Health Research, The University of Western Australia, Nedlands, WA, Australia.
authors.forename: E
authors.initials: E
authors.lastname: Kicic-Starcevich
authors.affiliation: Telethon Kids Institute, Centre for Health Research, The University of Western Australia, Nedlands, WA, Australia.
authors.forename: K-M
authors.initials: KM
authors.lastname: Ling
authors.affiliation: Telethon Kids Institute, Centre for Health Research, The University of Western Australia, Nedlands, WA, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Looi
authors.affiliation: Telethon Kids Institute, Centre for Health Research, The University of Western Australia, Nedlands, WA, Australia.
authors.forename: K M
authors.initials: KM
authors.lastname: Martinovich
authors.affiliation: Telethon Kids Institute, Centre for Health Research, The University of Western Australia, Nedlands, WA, Australia.
authors.forename: L W
authors.initials: LW
authors.lastname: Garratt
authors.affiliation: School of Paediatrics and Child Health, The University of Western Australia, Nedlands, WA, Australia.|Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, The University of Western Australia and Harry Perkins Institute of Medical Research, Nedlands, WA, Australia.
authors.forename: T
authors.initials: T
authors.lastname: Iosifidis
authors.affiliation: Telethon Kids Institute, Centre for Health Research, The University of Western Australia, Nedlands, WA, Australia.
authors.forename: N C
authors.initials: NC
authors.lastname: Shaw
authors.affiliation: Centre of Microscopy, Characterisation and Analysis, The University of Western Australia, Nedlands, WA, Australia.
authors.forename: A G
authors.initials: AG
authors.lastname: Buckley
authors.affiliation: Centre of Microscopy, Characterisation and Analysis, The University of Western Australia, Nedlands, WA, Australia.
authors.forename: P J
authors.initials: PJ
authors.lastname: Rigby
authors.affiliation: School of Medicine, Notre Dame University, Fremantle, WA, Australia.
authors.forename: F J
authors.initials: FJ
authors.lastname: Lannigan
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia.|Priority Research Centre for Asthma and Respiratory Disease, Hunter Medical Research Institute, Newcastle, NSW, Australia.|Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: D A
authors.initials: DA
authors.lastname: Knight
authors.affiliation: Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, WA, Australia.|School of Paediatrics and Child Health, The University of Western Australia, Nedlands, WA, Australia.|Telethon Kids Institute, Centre for Health Research, The University of Western Australia, Nedlands, WA, Australia.|Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, The University of Western Australia and Harry Perkins Institute of Medical Research, Nedlands, WA, Australia.
authors.forename: S M
authors.initials: SM
authors.lastname: Stick
mesh_terms: D000293:Adolescent; D000485:Allergens / Q000276:immunology; D017209:Apoptosis; D001249:Asthma / Q000150:complications* / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D002648:Child; D002675:Child, Preschool; D003139:Common Cold; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D010850:Picornaviridae Infections / Q000150:complications* / Q000378:metabolism / Q000821:virology; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D020545:Respiratory Mucosa / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D012229:Rhinovirus / Q000145:classification; D019562:Viral Load; D014779:Virus Replication
chemical_list: D000485:Allergens; D016207:Cytokines; D018836:Inflammation Mediators; D011991:Receptors, Virus; D007073:Immunoglobulin E
keywords: airway epithelium; asthma; human rhinovirus; wound repair