The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response.
Nat Immunol
; 15(8): 738-48, 2014 Aug.
Article
em En
| MEDLINE
| ID: mdl-24952504
ABSTRACT
Assembly of the NLRP3 inflammasome activates caspase-1 and mediates the processing and release of the leaderless cytokine IL-1ß and thereby serves a central role in the inflammatory response and in diverse human diseases. Here we found that upon activation of caspase-1, oligomeric NLRP3 inflammasome particles were released from macrophages. Recombinant oligomeric protein particles composed of the adaptor ASC or the p.D303N mutant form of NLRP3 associated with cryopyrin-associated periodic syndromes (CAPS) stimulated further activation of caspase-1 extracellularly, as well as intracellularly after phagocytosis by surrounding macrophages. We found oligomeric ASC particles in the serum of patients with active CAPS but not in that of patients with other inherited autoinflammatory diseases. Our findings support a model whereby the NLRP3 inflammasome, acting as an extracellular oligomeric complex, amplifies the inflammatory response.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Transporte
/
Caspase 1
/
Inflamassomos
/
Inflamação
/
Macrófagos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article