Interleukin-1ß Maturation Triggers Its Relocation to the Plasma Membrane for Gasdermin-D-Dependent and -Independent Secretion.
Cell Rep
; 24(6): 1425-1433, 2018 08 07.
Article
en En
| MEDLINE
| ID: mdl-30089254
ABSTRACT
IL-1ß requires processing by caspase-1 to generate the active, pro-inflammatory cytokine. Acute IL-1ß secretion from inflammasome-activated macrophages requires caspase-1-dependent GSDMD cleavage, which also induces pyroptosis. Mechanisms of IL-1ß 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-1ß from primary non-pyroptotic myeloid cells in vitro requires GSDMD, later IL-1ß release in vitro and in vivo proceeds independently of GSDMD. IL-1ß maturation is sufficient for slow, caspase-1/GSDMD-independent secretion of ectopic IL-1ß from resting, non-pyroptotic macrophages, but the speed of IL-1ß release is boosted by inflammasome activation, via caspase-1 and GSDMD. IL-1ß cleavage induces IL-1ß enrichment at PIP2-enriched plasma membrane ruffles, and this is a prerequisite for IL-1ß secretion and is mediated by a polybasic motif within the cytokine. We thus reveal a mechanism in which maturation-induced IL-1ß trafficking facilitates its unconventional secretion.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Membrana Celular
/
Proteínas de Unión a Fosfato
/
Péptidos y Proteínas de Señalización Intracelular
/
Interleucina-1beta
Límite:
Humans
Idioma:
En
Revista:
Cell Rep
Año:
2018
Tipo del documento:
Article
País de afiliación:
Australia