| First Author | Schneider KS | Year | 2017 |
| Journal | Cell Rep | Volume | 21 |
| Issue | 13 | Pages | 3846-3859 |
| PubMed ID | 29281832 | Mgi Jnum | J:268223 |
| Mgi Id | MGI:6272333 | Doi | 10.1016/j.celrep.2017.12.018 |
| Citation | Schneider KS, et al. (2017) The Inflammasome Drives GSDMD-Independent Secondary Pyroptosis and IL-1 Release in the Absence of Caspase-1 Protease Activity. Cell Rep 21(13):3846-3859 |
| abstractText | Inflammasomes activate the protease caspase-1, which cleaves interleukin-1beta and interleukin-18 to generate the mature cytokines and controls their secretion and a form of inflammatory cell death called pyroptosis. By generating mice expressing enzymatically inactive caspase-1(C284A), we provide genetic evidence that caspase-1 protease activity is required for canonical IL-1 secretion, pyroptosis, and inflammasome-mediated immunity. In caspase-1-deficient cells, caspase-8 can be activated at the inflammasome. Using mice either lacking the pyroptosis effector gasdermin D (GSDMD) or expressing caspase-1(C284A), we found that GSDMD-dependent pyroptosis prevented caspase-8 activation at the inflammasome. In the absence of GSDMD-dependent pyroptosis, the inflammasome engaged a delayed, alternative form of lytic cell death that was accompanied by the release of large amounts of mature IL-1 and contributed to host protection. Features of this cell death modality distinguished it from apoptosis, suggesting it may represent a distinct form of pro-inflammatory regulated necrosis. |
