SiO(2) and TiO(2) nanoparticles synergistically trigger macrophage inflammatory responses.
SiO(2) and TiO(2) nanoparticles synergistically trigger macrophage inflammatory responses.
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DOI：
10.1186/s12989-017-0192-6
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发表时间：
2017-04-11
影响因子：
10
通讯作者：
Nakayama M
中科院分区：
文献类型：
--
作者：
Tsugita M;Morimoto N;Nakayama M
二氧化硅（SiO2）纳米颗粒（NPs）和二氧化钛（TiO 2）纳米颗粒是应用最广泛的无机纳米材料。虽然SiO2和TiO 2纳米颗粒的单独毒性已被广泛研究，但这些纳米颗粒的联合毒性却知之甚少。在这项研究中，我们观察到在用SiO2和TiO 2纳米颗粒同时刺激的小鼠骨髓源性巨噬细胞中caspase-1炎性体的意外和剧烈活化和IL-1β的产生，所述SiO2和TiO 2纳米颗粒的浓度为这些纳米颗粒单独不引起巨噬细胞活化的浓度。与此相一致，在用SiO2和TiO 2 NP两者进行气管内治疗的小鼠中观察到显著的肺部炎症。在巨噬细胞中，位于溶酶体中的SiO2 NPs和TiO 2 NPs没有;而只有TiO 2 NPs产生ROS，这表明这些NPs诱导不同的细胞损伤，导致半胱天冬酶-1炎性体激活。有趣的是，动态光散射测量显示，尽管单个SiO2和TiO 2 NP立即聚集为微米尺寸，但这些NP的混合物在二价阳离子的存在下形成了稳定且相对单分散的复合物，其尺寸为~250 nm。总之，这些结果表明SiO2和TiO 2纳米颗粒协同诱导巨噬细胞炎症反应和随后的肺部炎症。因此，我们建议，重要的是要评估各种纳米材料组合的协同毒性。本文的在线版本（doi：10.1186/s12989-017-0192-6）包含补充材料，可供授权用户使用。
Silicon dioxide (SiO2) nanoparticles (NPs) and titanium dioxide (TiO2) NPs are the most widely used inorganic nanomaterials. Although the individual toxicities of SiO2 and TiO2 NPs have been extensively studied, the combined toxicity of these NPs is much less understood. In this study, we observed unexpected and drastic activation of the caspase-1 inflammasome and production of IL-1β in mouse bone marrow-derived macrophages stimulated simultaneously with SiO2 and TiO2 NPs at concentrations at which these NPs individually do not cause macrophage activation. Consistent with this, marked lung inflammation was observed in mice treated intratracheally with both SiO2 and TiO2 NPs. In macrophages, SiO2 NPs localized in lysosomes and TiO2 NPs did not; while only TiO2 NPs produced ROS, suggesting that these NPs induce distinct cellular damage leading to caspase-1 inflammasome activation. Intriguingly, dynamic light scattering measurements revealed that, although individual SiO2 and TiO2 NPs immediately aggregated to be micrometer size, the mixture of these NPs formed a stable and relatively monodisperse complex with a size of ~250 nm in the presence of divalent cations. Taken together, these results suggest that SiO2 and TiO2 NPs synergistically induce macrophage inflammatory responses and subsequent lung inflammation. Thus, we propose that it is important to assess the synergistic toxicity of various combinations of nanomaterials. The online version of this article (doi:10.1186/s12989-017-0192-6) contains supplementary material, which is available to authorized users.