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    DUSP10 negatively regulates the inflammatory response to Rhinovirus through IL-1β signalling.

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    Authors
    Manley, Grace C. A
    Stokes, Clare A
    Marsh, Elizabeth K. cc
    Sabroe, Ian
    Parker, Lisa C
    Affiliation
    University of Sheffield
    Issue Date
    2018-10-17
    
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    Show full item record
    Abstract
    Rhinoviral infection is a common trigger of the excessive inflammation observed during exacerbations of asthma and chronic obstructive pulmonary disease. Rhinovirus (RV) recognition by pattern recognition receptors activates the MAPK pathways, common inducers of inflammatory gene production. A family of dual-specificity phosphatases (DUSPs) can regulate MAPK function, but their roles in rhinoviral infection are not known. We hypothesised that DUSPs would negatively regulate the inflammatory response to RV infection. Our results revealed that p38 and JNK MAPKs play key roles in the inflammatory response of epithelial cells to RV infection. Three DUSPs previously shown to have roles in innate immunity, 1, 4 and 10, were expressed in primary bronchial epithelial cells, one of which, DUSP10, was down regulated by RV infection. Small interfering-RNA knock down of DUSP10 identified a role for the protein in negatively regulating inflammatory cytokine production in response to IL-1β alone and in combination with RV, without any effect on RV replication. This study identifies DUSP10 as an important regulator of airway inflammation in respiratory viral infection.Importance Rhinoviruses are one of the causes of the common cold. In patients with asthma or chronic obstructive pulmonary disease, viral infections, including rhinovirus, are the commonest cause of exacerbations. Novel therapeutics to limit viral inflammation are clearly required. The work presented here identifies DUSP10 as an important protein involved in limiting the inflammatory response in the airway without affecting immune control of the virus.
    Citation
    Manley, G.C.A. et al. (2018) ‘DUSP10 negatively regulates the inflammatory response to Rhinovirus through IL-1β signalling’, Journal of Virology. doi: 10.1128/JVI.01659-18
    Publisher
    American Society for Microbiology
    Journal
    Journal of Virology
    URI
    http://hdl.handle.net/10545/623178
    DOI
    10.1128/JVI.01659-18
    PubMed ID
    30333178
    Type
    Article
    Language
    en
    ISSN
    1098-5514
    ae974a485f413a2113503eed53cd6c53
    10.1128/JVI.01659-18
    Scopus Count
    Collections
    Human Sciences Research Centre

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