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Caspase-1 cleaves and activates the pro-inflammatory cytokine interleukin-1 beta (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.

Original publication




Journal article


Cell Death Differ

Publication Date





1827 - 1838


Animals, Caspase 1, Caspase 8, Cell Death, Cell Survival, DNA Gyrase, Embryo, Mammalian, Fibroblasts, Inflammasomes, Interleukin-1beta, Mice, Protein Multimerization, Recombinant Fusion Proteins