Title |
The intersection of cell death and inflammasome activation
|
---|---|
Published in |
Cellular and Molecular Life Sciences, April 2016
|
DOI | 10.1007/s00018-016-2205-2 |
Pubmed ID | |
Authors |
James E. Vince, John Silke |
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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 3 | 1% |
Brazil | 1 | <1% |
Unknown | 197 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 49 | 24% |
Researcher | 31 | 15% |
Student > Master | 28 | 14% |
Student > Doctoral Student | 18 | 9% |
Student > Bachelor | 13 | 6% |
Other | 34 | 17% |
Unknown | 28 | 14% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 45 | 22% |
Agricultural and Biological Sciences | 39 | 19% |
Immunology and Microbiology | 37 | 18% |
Medicine and Dentistry | 30 | 15% |
Neuroscience | 6 | 3% |
Other | 10 | 5% |
Unknown | 34 | 17% |