Activation of NLRP3 inflammasome by crystalline structures via cell surface contact
Activation of NLRP3 inflammasome by crystalline structures via cell surface contact
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晶体结构通过细胞表面接触激活 NLRP3 炎症小体
DOI：
10.1038/srep07281
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发表时间：
2014-12-02
影响因子：
4.6
通讯作者：
Shi, Yan
中科院分区：
文献类型：
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作者：
Hari, Aswin;Zhang, Yifei;Shi, Yan
晶体结构激活NLRP 3炎性体，导致IL-1 β的产生，然而，负责NLRP 3激活的分子相互作用尚未完全了解。组织蛋白酶B从破裂的吞噬溶酶体释放和钾离子流出已被认为是这种激活的关键。在这里，我们报告说，组织蛋白酶B再分布不是晶体诱导的IL-1 β产生的关键事件。具有未受干扰的溶酶体的二氧化硅和三聚氰酸盐晶体处理的巨噬细胞表现出ASC和半胱天冬酶-1的强共定位，指示NLRP 3炎性小体活化。重要的是，我们提供的证据表明，巨噬细胞膜与固定化晶体的结合足以诱导IL-1 β的释放，并且NLRP 3炎性体的这种激活通过阻断钾流出而被抑制。因此，这项工作揭示了晶体结构介导的NLRP 3炎性体调控的额外复杂性。
Crystalline structures activate the NLRP3 inflammasome, leading to the production of IL-1 beta, however, the molecular interactions responsible for NLRP3 activation are not fully understood. Cathepsin B release from the ruptured phagolysosome and potassium ion efflux have been suggested to be critical for this activation. Here, we report that Cathepsin B redistribution was not a crucial event in crystal-induced IL-1 beta production. Silica and monosodium urate crystal-treated macrophages with undisturbed lysosomes demonstrated strong co-localization of ASC and Caspase-1, indicative of NLRP3 inflammasome activation. Importantly, we provided evidence to suggest that macrophage cell membrane binding to immobilized crystals was sufficient to induce IL-1 beta release, and this activation of the NLRP3 inflammasome was inhibited by blocking potassium efflux. Therefore, this work reveals additional complexity in crystalline structure-mediated NLRP3 inflammasome regulations.