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Exogenous IFN-? has antiviral and anti-inflammatory properties in primary bronchial epithelial cells from asthmatic subjects exposed to rhinovirus

Record type: Article

Background: Rhinoviruses are the major cause of asthma exacerbations. Previous studies suggest that primary bronchial epithelial cells (PBECs) from asthmatic subjects are more susceptible to rhinovirus infection because of deficient IFN-? production. Although augmenting the innate immune response might provide a novel approach for treatment of virus-induced asthma exacerbations, the potential of IFN-? to modulate antiviral and proinflammatory responses in asthmatic epithelium is poorly characterized.

Objectives: We sought to compare responses of PBECs from nonasthmatic and asthmatic subjects to exogenous IFN-? and test the inflammatory effects of IFN-? in response to rhinovirus infection.

Methods: PBECs were treated with IFN-? and infected with a low inoculum of human rhinovirus serotype 1B to simulate a natural viral infection. Expression of interferon-responsive genes and inflammatory responses were analyzed by using reverse transcription–quantitative real-time PCR, cytometric bead arrays, or both; viral titers were assessed by using the 50% tissue culture infection dose.

Results: Expression of IFN-?–stimulated antiviral genes was comparable in PBECs from nonasthmatic or asthmatic donors. Exogenous IFN-? significantly protected PBECs from asthmatic donors against rhinovirus infection by suppressing viral replication. Interferon-inducible protein 10 (IP-10), RANTES, and IL-6 release in response to rhinovirus infection was triggered only in PBECs from asthmatic donors. Although exogenous IFN-? alone stimulated some release of IP-10 (but not IL-6 or RANTES), it significantly reduced rhinovirus-induced IP-10, RANTES, and IL-6 expression when tested in combination with rhinovirus.

Conclusions: PBECs from asthmatic donors have a normal antiviral response to exogenous IFN-?. The ability of IFN-? to suppress viral replication suggests that it might limit virus-induced exacerbations by shortening the duration of the inflammatory response.

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Citation

Cakebread, Julie A., Xu, Yunhe, Grainge, Chris, Kehagia, Valia, Howarth, Peter H., Holgate, Stephen T. and Davies, Donna E. (2011) Exogenous IFN-? has antiviral and anti-inflammatory properties in primary bronchial epithelial cells from asthmatic subjects exposed to rhinovirus Journal of Allergy and Clinical Immunology, 127, (5), 1148-1154.e9. (doi:10.1016/j.jaci.2011.01.023). (PMID:21329968).

More information

e-pub ahead of print date: 16 February 2011
Published date: May 2011
Keywords: innate immunity, picornaviridae infections, type i interferons, asthma exacerbation
Organisations: Infection Inflammation & Immunity

Identifiers

Local EPrints ID: 181697
URI: http://eprints.soton.ac.uk/id/eprint/181697
ISSN: 0091-6749
PURE UUID: 1020994d-03c1-40a2-a8df-e7b891b08395

Catalogue record

Date deposited: 19 Apr 2011 13:09
Last modified: 18 Jul 2017 11:58

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Contributors

Author: Julie A. Cakebread
Author: Yunhe Xu
Author: Chris Grainge
Author: Valia Kehagia
Author: Donna E. Davies

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