EGFR activation suppresses respiratory virus-induced IRF1-dependent CXCL10 production
| Autor: | Gundula Min-Oo, Benjamin T. Galen, Eric Ballon-Landa, Iris F. Ueki, Jay A. Nadel, Lewis L. Lanier, David S. Knoff, Jonathan L. Koff, April Kalinowski |
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| Rok vydání: | 2014 |
| Předmět: |
Chemokine
Rhinovirus Physiology viruses Respiratory System Medical Physiology medicine.disease_cause Influenza A Virus H1N1 Subtype Cell Movement Influenza A Virus 2.2 Factors relating to the physical environment 2.1 Biological and endogenous factors Killer Cells Aetiology Lung innate immunity biology CXCL10 Gefitinib Articles respiratory system Respiratory Syncytial Viruses Killer Cells Natural ErbB Receptors Infectious Diseases Virus Diseases Pneumonia & Influenza Respiratory Natural Respiratory virus Female Infection Signal Transduction Pulmonary and Respiratory Medicine Bronchi interferon regulatory factor 1 Virus Cell Line Immune system Physiology (medical) medicine Humans H1N1 Subtype Interleukin 8 Innate immune system Interleukin-8 Epithelial Cells Cell Biology Pneumonia Influenza Chemokine CXCL10 Emerging Infectious Diseases Immunology biology.protein Quinazolines Respiratory epithelium epidermal growth factor receptor Interferon Regulatory Factor-1 |
| Zdroj: | American journal of physiology. Lung cellular and molecular physiology, vol 307, iss 2 Kalinowski, A; Ueki, I; Min-Oo, G; Ballon-Landa, E; Knoff, D; Galen, B; et al.(2014). EGFR activation suppresses respiratory virus-induced IRF1-dependent CXCL10 production. American Journal of Physiology-Lung Cellular and Molecular Physiology, 307(2), L186-L196. doi: 10.1152/ajplung.00368.2013. UCSF: Retrieved from: http://www.escholarship.org/uc/item/9dd2t81m |
| Popis: | Airway epithelial cells are the primary cell type involved in respiratory viral infection. Upon infection, airway epithelium plays a critical role in host defense against viral infection by contributing to innate and adaptive immune responses. Influenza A virus, rhinovirus, and respiratory syncytial virus (RSV) represent a broad range of human viral pathogens that cause viral pneumonia and induce exacerbations of asthma and chronic obstructive pulmonary disease. These respiratory viruses induce airway epithelial production of IL-8, which involves epidermal growth factor receptor (EGFR) activation. EGFR activation involves an integrated signaling pathway that includes NADPH oxidase activation of metalloproteinase, and EGFR proligand release that activates EGFR. Because respiratory viruses have been shown to activate EGFR via this signaling pathway in airway epithelium, we investigated the effect of virus-induced EGFR activation on airway epithelial antiviral responses. CXCL10, a chemokine produced by airway epithelial cells in response to respiratory viral infection, contributes to the recruitment of lymphocytes to target and kill virus-infected cells. While respiratory viruses activate EGFR, the interaction between CXCL10 and EGFR signaling pathways is unclear, and the potential for EGFR signaling to suppress CXCL10 has not been explored. Here, we report that respiratory virus-induced EGFR activation suppresses CXCL10 production. We found that influenza virus-, rhinovirus-, and RSV-induced EGFR activation suppressed IFN regulatory factor (IRF) 1-dependent CXCL10 production. In addition, inhibition of EGFR during viral infection augmented IRF1 and CXCL10. These findings describe a novel mechanism that viruses use to suppress endogenous antiviral defenses, and provide potential targets for future therapies. © 2014 the American Physiological Society. |
| Databáze: | OpenAIRE |
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