Burkholderia cenocepacia is the causative agent of the fatal lung disease, Cepacia syndrome. Epithelial cells are the first cells challenged in airway infections, yet, their pro-inflammatory response to B. cenocepacia remains under investigated. Here, we aimed to determine pro-inflammatory mechanisms initiated by airway epithelial cells following B. cenocepacia infection. We first examined signaling pathways activated post B.cenocepacia infection, and found that phosphorylation of Erk, Akt, Iκk, and NF-κB occurred. Cytokine profiles showed that while epithelial cells secreted TNFα, IL-6, and IL-8, they did not secrete IL-1β. Strikingly, qRT-PCR showed significantly elevated mRNA levels of IL1b. Examination of IL-1β within cell lysates revealed pro-IL-1β was present at significant amounts, but the mature form failed to be secreted. This inability to secrete IL-1β was not specific to B. cenocepacia, as LPS stimulation showed similiar results. Caspase-1 is required for pro-IL-1β processing and mature IL-1β release. Interestingly, we found that caspase-1 was expressed at minimal levels in both mRNA and protein forms within epithelial cells. Transfection experiments showed that restoration of caspase-1 expression in epithelial cells permits IL-1β secretion. Our data show, for the first time, that deficiency of fundamental inflammasome components, particularly caspase-1, may be responsible for the lack of IL-1β secretion by infected epithelial cells.
- Copyright © 2013 by The American Association of Immunologists, Inc.