Cell death is not essential for caspase-1-mediated interleukin-1β activation and secretion
Date
2016
Authors
Conos, S.A.
Lawlor, K.E.
Vaux, D.L.
Vince, J.E.
Lindqvist, L.M.
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Journal article
Citation
Cell Death and Differentiation, 2016; 23(11):1827-1838
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Abstract
Caspase-1 cleaves and activates the pro-inflammatory cytokine interleukin-1β (IL-1β), yet the mechanism of IL-1β release and its dependence on cell death remains controversial. To address this issue, we generated a novel inflammasome independent system in which we directly activate caspase-1 by dimerization. In this system, caspase-1 dimerization induced the cleavage and secretion of IL-1β, which did not require processing of caspase-1 into its p20 and p10 subunits. Moreover, direct caspase-1 dimerization allowed caspase-1 activation of IL-1β to be separated from cell death.
Specifically, we demonstrate at the single cell level that IL-1β can be released from live, metabolically active, cells following caspase-1 activation. In addition, we show that dimerized or endogenous caspase-8 can also directly cleave IL-1β into its biologically active form, in the absence of canonical inflammasome components. Therefore, cell death is not obligatory for the robust secretion of bioactive IL-1β.
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Data source: Supplementary information, https://doi.org/10.1038/cdd.2016.69
Link to a related website: http://europepmc.org/articles/pmc5071572?pdf=render, Open Access via Unpaywall
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Copyright 2016 Springer Nature