| First Author | Aizawa E | Year | 2020 |
| Journal | iScience | Volume | 23 |
| Issue | 5 | Pages | 101070 |
| PubMed ID | 32361594 | Mgi Jnum | J:338648 |
| Mgi Id | MGI:6717683 | Doi | 10.1016/j.isci.2020.101070 |
| Citation | Aizawa E, et al. (2020) GSDME-Dependent Incomplete Pyroptosis Permits Selective IL-1alpha Release under Caspase-1 Inhibition. iScience 23(5):101070 |
| abstractText | Pyroptosis is a form of regulated cell death that is characterized by gasdermin processing and increased membrane permeability. Caspase-1 and caspase-11 have been considered to be essential for gasdermin D processing associated with inflammasome activation. In the present study, we found that NLRP3 inflammasome activation induces delayed necrotic cell death via ASC in caspase-1/11-deficient macrophages. Furthermore, ASC-mediated caspase-8 activation and subsequent gasdermin E processing are necessary for caspase-1-independent necrotic cell death. We define this necrotic cell death as incomplete pyroptosis because IL-1beta release, a key feature of pyroptosis, is absent, whereas IL-1alpha release is induced. Notably, unprocessed pro-IL-1beta forms a molecular complex to be retained inside pyroptotic cells. Moreover, incomplete pyroptosis accompanied by IL-1alpha release is observed under the pharmacological inhibition of caspase-1 with VX765. These findings suggest that caspase-1 inhibition during NLRP3 inflammasome activation modulates forms of cell death and permits the release of IL-1alpha from dying cells. |
