title: Analysis of human bronchial epithelial cell proinflammatory response to Burkholderia cenocepacia infection: inability to secrete il-1β.
abstract: Burkholderia cenocepacia, the causative agent of cepacia syndrome, primarily affects cystic fibrosis patients, often leading to death. In the lung, epithelial cells serve as the initial barrier to airway infections, yet their responses to B. cenocepacia have not been fully investigated. Here, we examined the molecular responses of human airway epithelial cells to B. cenocepacia infection. Infection led to early signaling events such as activation of Erk, Akt, and NF-κB. Further, TNFα, IL-6, IL-8, and IL-1β were all significantly induced upon infection, but no IL-1β was detected in the supernatants. Because caspase-1 is required for IL-1β processing and release, we examined its expression in airway epithelial cells. Interestingly, little to no caspase-1 was detectable in airway epithelial cells. Transfection of caspase-1 into airway epithelial cells restored their ability to secrete IL-1β following B. cenocepacia infection, suggesting that a deficiency in caspase-1 is responsible, at least in part, for the attenuated IL-1β secretion.
authors.affiliation: Integrated Biomedical Graduate Program, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Devyn D
authors.initials: DD
authors.lastname: Gillette
authors.forename: Prexy A
authors.initials: PA
authors.lastname: Shah
authors.forename: Thomas
authors.initials: T
authors.lastname: Cremer
authors.forename: Mikhail A
authors.initials: MA
authors.lastname: Gavrilin
authors.forename: Beth Y
authors.initials: BY
authors.lastname: Besecker
authors.forename: Anasuya
authors.initials: A
authors.lastname: Sarkar
authors.forename: Daren L
authors.initials: DL
authors.lastname: Knoell
authors.forename: Estelle
authors.initials: E
authors.lastname: Cormet-Boyaka
authors.forename: Mark D
authors.initials: MD
authors.lastname: Wewers
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Butchar
authors.forename: Susheela
authors.initials: S
authors.lastname: Tridandapani
mesh_terms: D001980:Bronchi / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D019121:Burkholderia Infections / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D057508:Burkholderia cenocepacia; D020170:Caspase 1 / Q000096:biosynthesis / Q000235:genetics; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D014162:Transfection
chemical_list: D016207:Cytokines; C508585:IL1B protein, human; D053583:Interleukin-1beta; D016328:NF-kappa B; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020170:Caspase 1