Caspase-1 Is an Apical Caspase Leading to Caspase-3 Cleavage in the AIM2 Inflammasome Response, Independent of Caspase-8.

Autor: Sagulenko V; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Qld 4072, Australia., Vitak N; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Qld 4072, Australia., Vajjhala PR; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Qld 4072, Australia., Vince JE; Walter and Eliza Hall Institute for Medical Research, Parkville, Vic 3052, Australia., Stacey KJ; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Qld 4072, Australia. Electronic address: katryn.stacey@uq.edu.au.
Jazyk: angličtina
Zdroj: Journal of molecular biology [J Mol Biol] 2018 Jan 19; Vol. 430 (2), pp. 238-247. Date of Electronic Publication: 2017 Oct 31.
DOI: 10.1016/j.jmb.2017.10.028
Abstrakt: Canonical inflammasomes are multiprotein complexes that can activate both caspase-1 and caspase-8. Caspase-1 drives rapid lysis of cells by pyroptosis and maturation of interleukin (IL)-1β and IL-18. In caspase-1-deficient cells, inflammasome formation still leads to caspase-3 activation and slower apoptotic death, dependent on caspase-8 as an apical caspase. A role for caspase-8 directly upstream of caspase-1 has also been suggested, but here we show that caspase-8-deficient macrophages have no defect in AIM2 inflammasome-mediated caspase-1 activation, pyroptosis, and IL-1β cleavage. In investigating the inflammasome-induced apoptotic pathway, we previously demonstrated that activated caspase-8 is essential for caspase-3 cleavage and apoptosis in caspase-1-deficient cells. However, here we found that AIM2 inflammasome-initiated caspase-3 cleavage was maintained in Ripk3 -/- Casp8 -/- macrophages. Gene knockdown showed that caspase-1 was required for the caspase-3 cleavage. Thus inflammasomes activate a network of caspases that can promote both pyroptotic and apoptotic cell death. In cells where rapid pyroptosis is blocked, delayed inflammasome-dependent cell death could still occur due to both caspase-1- and caspase-8-dependent apoptosis. Initiation of redundant cell death pathways is likely to be a strategy for coping with pathogen interference in death processes.
(Copyright © 2017 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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