DUSP10 negatively regulates the inflammatory response to Rhinovirus through IL-1β signalling.
AffiliationUniversity of Sheffield
MetadataShow full item record
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.
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.01659-18
PublisherAmerican Society for Microbiology
JournalJournal of Virology
- Rhinovirus infection causes steroid resistance in airway epithelium through nuclear factor κB and c-Jun N-terminal kinase activation.
- Authors: Papi A, Contoli M, Adcock IM, Bellettato C, Padovani A, Casolari P, Stanciu LA, Barnes PJ, Johnston SL, Ito K, Caramori G
- Issue date: 2013 Nov
- Emerging Regulatory Roles of Dual-Specificity Phosphatases in Inflammatory Airway Disease.
- Authors: Manley GCA, Parker LC, Zhang Y
- Issue date: 2019 Feb 5
- Novel immune genes associated with excessive inflammatory and antiviral responses to rhinovirus in COPD.
- Authors: Baines KJ, Hsu AC, Tooze M, Gunawardhana LP, Gibson PG, Wark PA
- Issue date: 2013 Feb 6
- Role of interleukin-1 and MyD88-dependent signaling in rhinovirus infection.
- Authors: Stokes CA, Ismail S, Dick EP, Bennett JA, Johnston SL, Edwards MR, Sabroe I, Parker LC
- Issue date: 2011 Aug
- The Dual-Specificity Phosphatase 10 (DUSP10): Its Role in Cancer, Inflammation, and Immunity.
- Authors: Jiménez-Martínez M, Stamatakis K, Fresno M
- Issue date: 2019 Apr 1