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Role of interleukin-1 and MyD88-dependent signaling in rhinovirus infection

Stokes, C.A., Ismail, S., Dick, E.P., Bennett, J.A., Johnston, S.L., Edwards, M.R., Sabroe, I. and Parker, L.C. (2011) Role of interleukin-1 and MyD88-dependent signaling in rhinovirus infection. Journal of Virology, 85 (15). pp. 7912-7921. ISSN 0022-538X

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Rhinoviral infection is an important trigger of acute inflammatory exacerbations in patients with underlying airway disease. We have previously established that interleukin-1 beta (IL-1 beta) is central in the communication between epithelial cells and monocytes during the initiation of inflammation. In this study we explored the roles of IL-1 beta and its signaling pathways in the responses of airway cells to rhinovirus-1B (RV-1B) and further determined how responses to RV-1B were modified in a model of bacterial coinfection. Our results revealed that IL-1 beta dramatically potentiated RV-1B-induced proinflammatory responses, and while monocytes did not directly amplify responses to RV-1B alone, they played an important role in the responses observed with our coinfection model. MyD88 is the essential signaling adapter for IL-1 beta and most Toll-like receptors. To examine the role of MyD88 in more detail, we created stable MyD88 knockdown epithelial cells using short hairpin RNA (shRNA) targeted to MyD88. We determined that IL-1 beta/MyD88 plays a role in regulating RV-1B replication and the inflammatory response to viral infection of airway cells. These results identify central roles for IL-1 beta and its signaling pathways in the production of CXCL8, a potent neutrophil chemoattractant, in viral infection. Thus, IL-1 beta is a viable target for controlling the neutrophilia that is often found in inflammatory airway disease and is exacerbated by viral infection of the airways.

Item Type: Article
Copyright, Publisher and Additional Information: © 2011 American Society for Microbiology. This is an author produced version of a paper subsequently published in Journal of Virology. Uploaded in accordance with the publisher's self-archiving policy.
Keywords: Bronchial Epithelial-Cells; OBSTRUCTIVE PULMONARY-DISEASE; Vascular Endothelial-Cells; Human Monocytic Cells; Airway Smooth-Muscle; Inflammatory Responses; Alveolar Macrophages; Gene Polymorphisms; Asthmatic Subjects; Immune-Response
Institution: The University of Sheffield
Academic Units: The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine (Sheffield)
Depositing User: Miss Anthea Tucker
Date Deposited: 02 Aug 2011 09:01
Last Modified: 08 Feb 2013 17:33
Published Version: http://dx.doi.org/10.1128/JVI.02649-10
Status: Published
Publisher: American Society for Microbiology
Refereed: Yes
Identification Number: 10.1128/JVI.02649-10
URI: http://eprints.whiterose.ac.uk/id/eprint/43178

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