NLRP3 炎性小体以颗粒状危险信号的形式释放，从而放大炎症反应。
The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response.
机构信息
1] Inflammation and Experimental Surgery Unit, CIBERehd, Institute for Bio-Health Research of Murcia, Clinical University Hospital Virgen de la Arrixaca, Murcia, Spain. [2].
Inflammation and Experimental Surgery Unit, CIBERehd, Institute for Bio-Health Research of Murcia, Clinical University Hospital Virgen de la Arrixaca, Murcia, Spain.
出版信息
Nat Immunol. 2014 Aug;15(8):738-48. doi: 10.1038/ni.2919. Epub 2014 Jun 22.
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.
NLRP3 炎性小体的组装激活了半胱天冬酶-1，并介导了无领袖细胞因子 IL-1β 的加工和释放，从而在炎症反应和多种人类疾病中发挥核心作用。在这里，我们发现 caspase-1 激活后，寡聚 NLRP3 炎性小体颗粒从巨噬细胞中释放出来。由衔接蛋白 ASC 或与 Cryopyrin 相关周期性综合征 (CAPS) 相关的 NLRP3 p.D303N 突变体形式组成的重组寡聚蛋白颗粒在体外刺激 caspase-1 的进一步激活，并且在被周围巨噬细胞吞噬后在细胞内也能激活。我们在患有活性 CAPS 的患者的血清中发现了寡聚 ASC 颗粒，但在患有其他遗传性自身炎症性疾病的患者的血清中没有发现。我们的发现支持这样一种模型，即 NLRP3 炎性小体作为一种细胞外的寡聚复合物，放大了炎症反应。
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