Background

Silica dioxide nanoparticles (SiONPs) have been used for various medical applications, including therapeutics and imaging, and the use of SiONPs has increased gradually over the years. However, despite an increase in the use of SiONPs, not much is known about mechanism of action of SiONPs and their pulmonary toxicity.

Objective

The present study investigated the pulmonary toxicity of SiONPs and explored the underlying mechanism of action, primarily focusing on thioredoxin-interacting protein (TXNIP)/NOD-like receptor pyrin domain-containing 3 (NLRP3) in SiONPs-treated mice. We investigated the toxic effects of SiONPs in the lung of BALB/c mice administered 5, 10, and 20 mg/kg SiONPs for 3 days.

Results

Exposure to SiONPs markedly increased inflammatory cell counts, including those of neutrophils and macrophages, and levels of inflammatory mediators, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in a dose-dependent manner in the bronchoalveolar lavage fluid. Moreover, the inflammation was verified upon histopathological analysis. In addition, exposure to SiONPs increased the expression of TXNIP in a dose-dependent manner and, in turn, upregulated NLRP3 inflammasome proteins, which subsequently induced IL-1β production.

Conclusion

Collectively, exposure to SiONPs induced inflammation in the lungs of mice, which resulted in the activation of IL-1β production via the TXNIP-NLRP3 axis. Our results provide useful information on the pulmonary toxicity induced by SiONPs and provide insights into the underlying mechanism of action.

中文翻译：

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通过TXNIP / NLRP3信号通路的二氧化硅纳米颗粒引起的小鼠肺部炎症

背景

二氧化硅纳米粒子（SiONPs）已用于各种医疗应用，包括治疗和成像，并且多年来SiONPs的使用逐渐增加。但是，尽管增加了SiONP的使用，但对SiONP的作用机理及其肺毒性了解不多。

目的

本研究调查了SiONPs的肺毒性，并探讨了其潜在的作用机理，主要集中在SiONPs处理的小鼠中，硫氧还蛋白相互作用蛋白（TXNIP）/ NOD样受体含吡啶结构域3（NLRP3）。我们调查了SiONPs对施用5、10和20 mg / kg SiONPs的BALB / c小鼠的肺部毒性，持续3天。

结果

暴露于SiONPs时，支气管肺泡中的炎症细胞计数显着增加，包括中性粒细胞和巨噬细胞的炎症细胞计数以及白介素（IL）-1β，IL-6和肿瘤坏死因子-α等炎症介质的水平。灌洗液。此外，通过组织病理学分析证实了炎症。另外，暴露于SiONPs以剂量依赖性方式增加TXNIP的表达，进而上调NLRP3炎性小体蛋白，随后诱导IL-1β的产生。

结论

集体地，暴露于SiONPs会诱发小鼠肺部炎症，从而导致通过TXNIP-NLRP3轴激活IL-1β的产生。我们的结果提供了有关SiONPs诱导的肺毒性的有用信息，并提供了对潜在作用机理的见解。