The intersection of cell death and inflammasome activation
- Journal Title
- Cell Mol Life Sci
- Publication Type
- Journal Article in press
- Abstract
- Inflammasomes sense cellular danger to activate the cysteine-aspartic protease caspase-1, which processes precursor interleukin-1beta (IL-1beta) 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-1beta activation and cell death is further highlighted by research showing that the extrinsic apoptotic caspase, caspase-8, may, like caspase-1, directly process IL-1beta, 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-1beta inflammatory responses in vivo. Here, we review the mechanisms by which cell death signaling activates inflammasomes to initiate IL-1beta-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-1beta secretion and evaluate studies suggesting that several cell death regulatory proteins can directly interact with, and modulate the function of, inflammasome and IL-1beta containing protein complexes.
- Publisher
- Springer
- Research Division(s)
- Inflammation; Cell Signalling And Cell Death
- PubMed ID
- 27066895
- Publisher's Version
- https://doi.org/10.1007/s00018-016-2205-2
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2016-04-28 02:07:01
Last Modified: 2016-05-02 09:52:16