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dc.contributor.authorManley, Grace C. A
dc.contributor.authorStokes, Clare A
dc.contributor.authorMarsh, Elizabeth K.
dc.contributor.authorSabroe, Ian
dc.contributor.authorParker, Lisa C
dc.date.accessioned2018-12-05T15:06:23Z
dc.date.available2018-12-05T15:06:23Z
dc.date.issued2018-10-17
dc.identifier.citationManley, 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.01659-18en
dc.identifier.issn1098-5514
dc.identifier.pmid30333178
dc.identifier.doi10.1128/JVI.01659-18
dc.identifier.urihttp://hdl.handle.net/10545/623178
dc.description.abstractRhinoviral 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.
dc.description.sponsorshipThis work was funded by a University of Sheffield, Medicine, Dentistry and Health faculty scholarship and a New Investigator Research Grant from the Medical Research Council, reference MR/J010154/1en
dc.language.isoenen
dc.publisherAmerican Society for Microbiologyen
dc.rightsArchived with thanks to Journal of virologyen
dc.subjectRhinovirusen
dc.subjectDUSP10en
dc.subjectInnate Immunityen
dc.titleDUSP10 negatively regulates the inflammatory response to Rhinovirus through IL-1β signalling.en
dc.typeArticleen
dc.contributor.departmentUniversity of Sheffielden
dc.identifier.journalJournal of Virologyen
html.description.abstractRhinoviral 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.


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