Cell death is not essential for caspase-1-mediated interleukin-1beta activation and secretion
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
WEHI Research Division(s)
Inflammation; Cell Signalling And Cell Death
PubMed ID
27419363
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
An error has occurred. This application may no longer respond until reloaded. Reload 🗙