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Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus

Title: Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus
Author(s): Wark, PAB
Johnston, SL
Bucchieri, F
Powell, R
Puddicombe, S
Laza-Stanca, V
Holgate, ST
Davies, DE
Item Type: Journal Article
Abstract: Rhinoviruses are the major trigger of acute asthma exacerbations and asthmatic subjects are more susceptible to these infections. To investigate the underlying mechanisms of this increased susceptibility, we examined virus replication and innate responses to rhinovirus (RV)-16 infection of primary bronchial epithelial cells from asthmatic and healthy control subjects. Viral RNA expression and late virus release into supernatant was increased 50- and 7-fold, respectively in asthmatic cells compared with healthy controls. Virus infection induced late cell lysis in asthmatic cells but not in normal cells. Examination of the early cellular response to infection revealed impairment of virus induced caspase 3/7 activity and of apoptotic responses in the asthmatic cultures. Inhibition of apoptosis in normal cultures resulted in enhanced viral yield, comparable to that seen in infected asthmatic cultures. Examination of early innate immune responses revealed profound impairment of virus-induced interferon-β mRNA expression in asthmatic cultures and they produced >2.5 times less interferon-β protein. In infected asthmatic cells, exogenous interferon-β induced apoptosis and reduced virus replication, demonstrating a causal link between deficient interferon-β, impaired apoptosis and increased virus replication. These data suggest a novel use for type I interferons in the treatment or prevention of virus-induced asthma exacerbations.
Publication Date: 21-Mar-2005
Date of Acceptance: 24-Dec-2004
URI: http://hdl.handle.net/10044/1/41542
DOI: 10.1084/jem.20041901
ISSN: 1540-9538
Publisher: Rockefeller University Press
Start Page: 937
End Page: 947
Journal / Book Title: Journal of Experimental Medicine
Volume: 201
Issue: 6
Sponsor/Funder: British Medical Association
Funder's Grant Number: DPA/nj
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
Medicine, Research & Experimental
Research & Experimental Medicine
IMMUNOLOGY
MEDICINE, RESEARCH & EXPERIMENTAL
INHALED CORTICOSTEROIDS
LOWER AIRWAYS
EXACERBATIONS
RECEPTOR
TRANSCRIPTION
INFLAMMATION
EXPRESSION
CHILDREN
VIRUSES
KINASE
Adult
Antiviral Agents
Apoptosis
Asthma
Bronchi
Caspase 3
Caspase 7
Caspases
Cells, Cultured
Epithelial Cells
Female
Gene Expression Regulation
Humans
Immunity, Innate
Interferon-beta
Male
Middle Aged
Picornaviridae Infections
RNA, Viral
Rhinovirus
Virus Replication
Bronchi
Cells, Cultured
Epithelial Cells
Humans
Rhinovirus
Picornaviridae Infections
Asthma
Caspases
Interferon-beta
RNA, Viral
Antiviral Agents
Virus Replication
Apoptosis
Gene Expression Regulation
Adult
Middle Aged
Female
Male
Caspase 3
Caspase 7
Immunity, Innate
Immunology
11 Medical And Health Sciences
Publication Status: Published
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine



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