| First Author | Monteleone M | Year | 2018 |
| Journal | Cell Rep | Volume | 24 |
| Issue | 6 | Pages | 1425-1433 |
| PubMed ID | 30089254 | Mgi Jnum | J:271305 |
| Mgi Id | MGI:6279133 | Doi | 10.1016/j.celrep.2018.07.027 |
| Citation | Monteleone M, et al. (2018) Interleukin-1beta Maturation Triggers Its Relocation to the Plasma Membrane for Gasdermin-D-Dependent and -Independent Secretion. Cell Rep 24(6):1425-1433 |
| abstractText | IL-1beta requires processing by caspase-1 to generate the active, pro-inflammatory cytokine. Acute IL-1beta secretion from inflammasome-activated macrophages requires caspase-1-dependent GSDMD cleavage, which also induces pyroptosis. Mechanisms of IL-1beta secretion by pyroptotic and non-pyroptotic cells, and the precise functions of caspase-1 and GSDMD therein, are unresolved. Here, we show that, while efficient early secretion of endogenous IL-1beta from primary non-pyroptotic myeloid cells in vitro requires GSDMD, later IL-1beta release in vitro and in vivo proceeds independently of GSDMD. IL-1beta maturation is sufficient for slow, caspase-1/GSDMD-independent secretion of ectopic IL-1beta from resting, non-pyroptotic macrophages, but the speed of IL-1beta release is boosted by inflammasome activation, via caspase-1 and GSDMD. IL-1beta cleavage induces IL-1beta enrichment at PIP2-enriched plasma membrane ruffles, and this is a prerequisite for IL-1beta secretion and is mediated by a polybasic motif within the cytokine. We thus reveal a mechanism in which maturation-induced IL-1beta trafficking facilitates its unconventional secretion. |
