In:
The Journal of Immunology, The American Association of Immunologists, Vol. 190, No. 1_Supplement ( 2013-05-01), p. 56.15-56.15
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.190.Supp.56.15
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2013
detail.hit.zdb_id:
1475085-5
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