EPA Science Inventory

Influenza enhances caspase-1 in bronchial epithelial cells from asthmatic volunteers and is associated with pathogenesis

Citation:

Bauer, R., L. Brighton, L. Mueller, Z. Xiang, J. Rager, R. Fry, D. Peden, AND I. Jaspers. Influenza enhances caspase-1 in bronchial epithelial cells from asthmatic volunteers and is associated with pathogenesis. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. Journal of Allergy Clinical Immunology, 130(4):958-67, (2012).

Description:

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 A virus. An inflainmasome-spedflc quantitative realtime 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-l and PYCARD colocalization. Tracheal epithelial cells from caspase-1--deflcient 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 ILB , IL-6, and TNF-a. Specifically, influenza-induced caspase-l 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.

Purpose/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.

URLs/Downloads:

Record Details:

Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Start Date: 10/01/2012
Completion Date: 10/01/2012
Record Last Revised: 03/26/2013
Record Created: 03/22/2013
Record Released: 03/22/2013
OMB Category: Other
Record ID: 253693

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB

ENVIRONMENTAL PUBLIC HEALTH DIVISION