期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 130, 期 4, 页码 958-+出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2012.07.013
关键词
Epithelial cell; asthma; influenza; antiviral; inflammasome; caspase-1; innate immunity
资金
- National Institute for Allergy and Infectious Diseases [U19A1O77347]
- National Institute of Environmental Health Sciences [ES013611]
- US Environmental Protection Agency through Center for Environmental Medicine, Asthma, and Lung Biology at The University of North Carolina at Chapel Hill [CR83346301]
- Swiss National Science Foundation
- National Institute of Allergy and Infectious Diseases/National Institutes of Health (NIH)
- MedImmune
- US Environmental Protection Agency
- Aquinox Pharmaceuticals
- NIH
- Flight Attendant Medical Research Institute (FAMRI)
Background: The leading cause of asthma exacerbation is respiratory viral infection. Innate antiviral defense pathways are altered in the asthmatic epithelium, yet involvement of inflammasome signaling in virus-induced asthma exacerbation is not known. Objective: This study compared influenza-induced activation of inflammasome and innate immune signaling in human bronchial epithelial cells from volunteers with and without asthma and investigated the role of caspase-1 in epithelial cell antiviral defense. Methods: Differentiated primary human bronchial epithelial cells from volunteers with and without asthma were infected with influenza Avirus. An inflammasome-specific quantitative real-time polymerase chain reaction array was used to compare baseline and influenza-induced gene expression profiles. Cytokine secretion, innate immune gene expression, and viral replication were compared between human bronchial epithelial cells from volunteers with and without asthma. Immunofluorescence microscopy was used to evaluate caspase-1 and PYCARD colocalization. Tracheal epithelial cells from caspase-1-deficient or wild-type mice were infected with influenza and assessed for antiviral gene expression and viral replication. Results: Human bronchial epithelial cells from asthmatic volunteers had altered influenza-induced expression of inflammasome-related and innate immune signaling components, which correlated with enhanced production of IL-1 beta, IL-6, and TNF-alpha. Specifically, influenza-induced caspase-1 expression was enhanced and localization differed in human bronchial epithelial cells from asthmatic volunteers compared to volunteers without asthma. Influenza-infected tracheal epithelial cells from caspase-1-deficient mice had reduced expression of antiviral genes and viral replication. Conclusion: Caspase-1 plays an important role in the airway epithelial cell response to influenza infection, which is enhanced in asthmatic volunteers, and may contribute to the enhanced influenza-related pathogenesis observed in vivo. (J Allergy Clin Immunol 2012; 130: 958-67.)
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