Cell death is not essential for caspase-1-mediated interleukin-1? activation and secretion.

ABSTRACT: Caspase-1 cleaves and activates the pro-inflammatory cytokine interleukin-1 beta (IL-1?), yet the mechanism of IL-1? 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-1?, 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-1? to be separated from cell death. Specifically, we demonstrate at the single cell level that IL-1? 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-1? 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-1?.

SUBMITTER: Conos SA 

PROVIDER: S-EPMC5071572 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature