| First Author | Tsuchiya K | Year | 2021 |
| Journal | Cell Rep | Volume | 34 |
| Issue | 12 | Pages | 108887 |
| PubMed ID | 33761363 | Mgi Jnum | J:324672 |
| Mgi Id | MGI:6716777 | Doi | 10.1016/j.celrep.2021.108887 |
| Citation | Tsuchiya K, et al. (2021) Gasdermin D mediates the maturation and release of IL-1alpha downstream of inflammasomes. Cell Rep 34(12):108887 |
| abstractText | IL-1alpha serves as a pro-inflammatory cytokine. Although pro-IL-1alpha has cytokine activity, proteolytic maturation increases its potency and release from cells. IL-1alpha maturation occurs in a caspase-1-dependent manner following inflammasome activation. However, pro-IL-1alpha is not a substrate of caspase-1, and it remains unclear what mediates the maturation of this cytokine downstream of inflammasomes. Here, we show that gasdermin D (GSDMD), an executor of pyroptosis, is required for the rapid induction of IL-1alpha maturation by non-particulate inflammasome activators. Ablation of GSDMD abrogates the maturation of IL-1alpha, but not of IL-1beta. Inflammasome-induced maturation of IL-1alpha relies on extracellular Ca(2+) and calpains. Ca(2+) influx and calpain activation are induced in a GSDMD-dependent manner. Glycine, which inhibits cell lysis, but not GSDMD pore formation, does not affect IL-1alpha maturation. These results suggest that during inflammasome activation, GSDMD processed by caspase-1 forms plasma membrane pores that mediate Ca(2+) influx, resulting in the calpain-dependent maturation of IL-1alpha. |
