The NLRP3 Inflammasome is Released As a Particulate Danger Signal That Amplifies the Inflammatory Response

Overview

Journal Nat Immunol

Date 2014 Jun 23

PMID 24952504

Citations 431

Authors

Alberto Baroja-Mazo

Fatima Martin-Sanchez

Ana I Gomez

Carlos M Martinez

Joaquin Amores-Iniesta

Vincent Compan

Maria Barbera-Cremades

Jordi Yague

Estibaliz Ruiz-Ortiz

Jordi Anton

Segundo Bujan

Isabelle Couillin

David Brough

Juan I Arostegui

Pablo Pelegrin

Affiliations

Soon will be listed here.

Abstract

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.

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