1. Analysis of human bronchial epithelial cell proinflammatory response to Burkholderia cenocepacia infection: inability to secrete il-1β.
- Author
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Gillette DD, Shah PA, Cremer T, Gavrilin MA, Besecker BY, Sarkar A, Knoell DL, Cormet-Boyaka E, Wewers MD, Butchar JP, and Tridandapani S
- Subjects
- Bronchi microbiology, Bronchi pathology, Burkholderia Infections genetics, Burkholderia Infections microbiology, Burkholderia Infections pathology, Caspase 1 biosynthesis, Caspase 1 genetics, Cell Line, Cytokines biosynthesis, Cytokines genetics, Epithelial Cells microbiology, Epithelial Cells pathology, Extracellular Signal-Regulated MAP Kinases genetics, Extracellular Signal-Regulated MAP Kinases metabolism, Humans, Interleukin-1beta genetics, NF-kappa B genetics, NF-kappa B metabolism, Proto-Oncogene Proteins c-akt genetics, Proto-Oncogene Proteins c-akt metabolism, Respiratory Mucosa microbiology, Respiratory Mucosa pathology, Transfection, Bronchi metabolism, Burkholderia Infections metabolism, Burkholderia cenocepacia, Epithelial Cells metabolism, Interleukin-1beta metabolism, Respiratory Mucosa metabolism
- 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.
- Published
- 2013
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