Cell death is not essential for caspase-1-mediated interleukin-1beta activation and secretion
- Author(s)
- Conos, SA; Lawlor, KE; Vaux, DL; Vince, JE; Lindqvist, LM;
- Details
- Publication Year 2016-07-15,Volume 23,Issue #11,Page 1827-1838
- Journal Title
- Cell Death and Differentiation
- Publication Type
- Journal Article
- Abstract
- 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.Cell Death and Differentiation advance online publication, 15 July 2016; doi:10.1038/cdd.2016.69.
- Publisher
- NPG
- Research Division(s)
- Inflammation; Cell Signalling And Cell Death
- PubMed ID
- 27419363
- Link To PubMed Central Version
- https://www-ncbi-nlm-nih-gov/pmc/articles/PMC5071572/
- Publisher's Version
- https://doi.org/10.1038/cdd.2016.69
- NHMRC Grants
- NHMRC/1051210, NHMRC/1101405, NHMRC/1052598, NHMRC/1035502, NHMRC/1020136, NHMRC/461221,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2016-08-10 04:12:51
Last Modified: 2017-12-15 11:59:50