| First Author | Conos SA | Year | 2016 |
| Journal | Cell Death Differ | Volume | 23 |
| Issue | 11 | Pages | 1827-1838 |
| PubMed ID | 27419363 | Mgi Jnum | J:258526 |
| Mgi Id | MGI:6140472 | Doi | 10.1038/cdd.2016.69 |
| Citation | Conos SA, et al. (2016) Cell death is not essential for caspase-1-mediated interleukin-1beta activation and secretion. Cell Death Differ 23(11):1827-1838 |
| abstractText | Caspase-1 cleaves and activates the pro-inflammatory cytokine interleukin-1 beta (IL-1beta), yet the mechanism of IL-1beta 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-1beta, 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-1beta to be separated from cell death. Specifically, we demonstrate at the single cell level that IL-1beta 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-1beta 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-1beta. |
