Stokes, C.A., Ismail, S., Dick, E.P. et al. (5 more authors) (2011) Role of interleukin-1 and MyD88-dependent signaling in rhinovirus infection. Journal of Virology, 85 (15). pp. 7912-7921. ISSN 0022-538X
Abstract
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.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
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 |
Dates: |
|
Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (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 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:43178 |
Downloads
Filename: WRRO_43178.pdf
Description: Main Article
Filename: WRRO_43178_Supplementary.pdf
Description: Supplementary Figures