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Cell Mol Life Sci. 2016 Jun;73(11-12):2349-67. doi: 10.1007/s00018-016-2205-2. Epub 2016 Apr 11.

The intersection of cell death and inflammasome activation.

Author information

1
The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia. vince@wehi.edu.au.
2
Department of Medical Biology, The University of Melbourne, Parkville, VIC, 3050, Australia. vince@wehi.edu.au.
3
The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.
4
Department of Medical Biology, The University of Melbourne, Parkville, VIC, 3050, Australia.

Abstract

Inflammasomes sense cellular danger to activate the cysteine-aspartic protease caspase-1, which processes precursor interleukin-1β (IL-1β) and IL-18 into their mature bioactive fragments. In addition, activated caspase-1 or the related inflammatory caspase, caspase-11, can cleave gasdermin D to induce a lytic cell death, termed pyroptosis. The intertwining of IL-1β activation and cell death is further highlighted by research showing that the extrinsic apoptotic caspase, caspase-8, may, like caspase-1, directly process IL-1β, activate the NLRP3 inflammasome itself, or bind to inflammasome complexes to induce apoptotic cell death. Similarly, RIPK3- and MLKL-dependent necroptotic signaling can activate the NLRP3 inflammasome to drive IL-1β inflammatory responses in vivo. Here, we review the mechanisms by which cell death signaling activates inflammasomes to initiate IL-1β-driven inflammation, and highlight the clinical relevance of these findings to heritable autoinflammatory diseases. We also discuss whether the act of cell death can be separated from IL-1β secretion and evaluate studies suggesting that several cell death regulatory proteins can directly interact with, and modulate the function of, inflammasome and IL-1β containing protein complexes.

KEYWORDS:

Apoptosis; Caspase-1; Caspase-8; Inflammasome; MLKL; Necroptosis; Pyroptosis; RIPK3

PMID:
27066895
DOI:
10.1007/s00018-016-2205-2
[Indexed for MEDLINE]

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