title: Influenza enhances caspase-1 in bronchial epithelial cells from asthmatic volunteers and is associated with pathogenesis.
abstract: 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 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-1β, IL-6, and TNF-α. 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Curriculum in Toxicology, Gillings School of Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Rebecca N
authors.initials: RN
authors.lastname: Bauer
authors.forename: Luisa E
authors.initials: LE
authors.lastname: Brighton
authors.forename: Loretta
authors.initials: L
authors.lastname: Mueller
authors.forename: Zhidan
authors.initials: Z
authors.lastname: Xiang
authors.forename: Julia E
authors.initials: JE
authors.lastname: Rager
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Fry
authors.forename: David B
authors.initials: DB
authors.lastname: Peden
authors.forename: Ilona
authors.initials: I
authors.lastname: Jaspers
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001249:Asthma / Q000209:etiology / Q000276:immunology*; D001980:Bronchi / Q000276:immunology*; D053468:CARD Signaling Adaptor Proteins; D020170:Caspase 1 / Q000032:analysis / Q000502:physiology*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000032:analysis; D004847:Epithelial Cells / Q000276:immunology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007251:Influenza, Human / Q000150:complications*; D053583:Interleukin-1beta / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D014779:Virus Replication
chemical_list: D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins; D053583:Interleukin-1beta; C498534:Pycard protein, mouse; D020170:Caspase 1