Reference - Detail
| RRC ID | 67830 |
|---|---|
| Author | Tsuchiya K, Hosojima S, Hara H, Kushiyama H, Mahib MR, Kinoshita T, Suda T. |
| Title | Gasdermin D mediates the maturation and release of IL-1α downstream of inflammasomes. |
| Journal | Cell Rep |
| Abstract |
IL-1α serves as a pro-inflammatory cytokine. Although pro-IL-1α has cytokine activity, proteolytic maturation increases its potency and release from cells. IL-1α maturation occurs in a caspase-1-dependent manner following inflammasome activation. However, pro-IL-1α 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-1α maturation by non-particulate inflammasome activators. Ablation of GSDMD abrogates the maturation of IL-1α, but not of IL-1β. Inflammasome-induced maturation of IL-1α relies on extracellular Ca2+ and calpains. Ca2+ 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-1α maturation. These results suggest that during inflammasome activation, GSDMD processed by caspase-1 forms plasma membrane pores that mediate Ca2+ influx, resulting in the calpain-dependent maturation of IL-1α. |
| Volume | 34(12) |
| Pages | 108887 |
| Published | 2021-3-23 |
| DOI | 10.1016/j.celrep.2021.108887 |
| PII | S2211-1247(21)00201-1 |
| PMID | 33761363 |
| MeSH | Animals Calcium / metabolism Calpain / metabolism Caspase 1 / metabolism Cell Shape Enzyme Activation Humans Inflammasomes / metabolism* Interleukin-1alpha / metabolism* Intracellular Signaling Peptides and Proteins / deficiency Intracellular Signaling Peptides and Proteins / metabolism* Macrophages / metabolism* Mice Mice, Inbred C57BL Phosphate-Binding Proteins / deficiency Phosphate-Binding Proteins / metabolism* Proteolysis* RAW 264.7 Cells THP-1 Cells |
| IF | 8.109 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 37 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | RAW 264(RCB0535) |