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KMID : 1034820200160030245
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Molecular & Cellular Toxicology
2020 Volume.16 No. 3 p.245 ~ p.252
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Pulmonary inflammation caused by silica dioxide nanoparticles in mice via TXNIP/NLRP3 signaling pathway
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Lim Je-Oh
Ko Je-Won
Jung Tae-Yang
Kim Woong-Il
Pak So-Won
Shin In-Sik
Yun Won-Kee
Kim Hyoung-Chin
Heo Jeong-Doo
Kim Jong-Choon
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Abstract
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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.
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KEYWORD
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Silica dioxide nanoparticle, Inflammation, Thioredoxin-interacting protein, NOD-like receptor pyrin domain-containing 3 inflammasome
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