TY - JOUR
T1 - The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response
AU - Baroja-Mazo, Alberto
AU - Martín-Sánchez, Fatima
AU - Gomez, Ana I.
AU - Martínez, Carlos M.
AU - Amores-Iniesta, Joaquín
AU - Compan, Vincent
AU - Barberà-Cremades, Maria
AU - Yagüe, Jordi
AU - Ruiz-Ortiz, Estibaliz
AU - Antón, Jordi
AU - Buján, Segundo
AU - Couillin, Isabelle
AU - Brough, David
AU - Arostegui, Juan I.
AU - Pelegrín, Pablo
PY - 2014/6/22
Y1 - 2014/6/22
N2 - Assembly of the NLRP3 inflammasome activates caspase-1 and mediates the processing and release of the leaderless cytokine IL-1β 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. © 2014 Nature America, Inc. All rights reserved.
AB - Assembly of the NLRP3 inflammasome activates caspase-1 and mediates the processing and release of the leaderless cytokine IL-1β 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. © 2014 Nature America, Inc. All rights reserved.
U2 - 10.1038/ni.2919
DO - 10.1038/ni.2919
M3 - Article
SN - 1529-2916
VL - 15
SP - 738
EP - 748
JO - Nature Immunology
JF - Nature Immunology
IS - 8
ER -