DUSP10 Negatively Regulates the Inflammatory Response to Rhinovirus through Interleukin-1β Signaling
| العنوان: | DUSP10 Negatively Regulates the Inflammatory Response to Rhinovirus through Interleukin-1β Signaling |
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| المؤلفون: | Clare A. Stokes, Lisa C. Parker, Ian Sabroe, Elizabeth K. Marsh, Grace C. A. Manley |
| المصدر: | Journal of Virology |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | MAPK/ERK pathway, Rhinovirus, MAP Kinase Signaling System, medicine.medical_treatment, viruses, Immunology, Interleukin-1beta, Down-Regulation, Cellular Response to Infection, Inflammation, Bronchi, Biology, medicine.disease_cause, Microbiology, 03 medical and health sciences, 0302 clinical medicine, Virology, medicine, Humans, COPD, Protein kinase A, Cells, Cultured, 030304 developmental biology, 0303 health sciences, Innate immune system, lung infection, Kinase, asthma/allergy, Pattern recognition receptor, Epithelial Cells, respiratory system, 3. Good health, respiratory tract diseases, Cytokine, IL-1β, inflammation, 030220 oncology & carcinogenesis, Insect Science, Gene Knockdown Techniques, Dual-Specificity Phosphatases, Mitogen-Activated Protein Kinase Phosphatases, medicine.symptom |
| الوصف: | Rhinoviruses are one of the causes of the common cold. In patients with asthma or chronic obstructive pulmonary disease, viral infections, including those with 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. 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 mitogen-activated protein kinase (MAPK) pathways, which are 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 hypothesized that DUSPs would negatively regulate the inflammatory response to RV infection. Our results revealed that the p38 and c-Jun N-terminal kinase (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 (DUSPs 1, 4, and 10) were expressed in primary bronchial epithelial cells, and one of them, DUSP10, was downregulated by RV infection. Small interfering RNA-mediated knockdown of DUSP10 identified a role for the protein in negatively regulating inflammatory cytokine production in response to interleukin-1β (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 those with 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. |
| تدمد: | 1098-5514 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::93ffb972cfac8f724313da6256843121 https://pubmed.ncbi.nlm.nih.gov/30333178 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....93ffb972cfac8f724313da6256843121 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10985514 |
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