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Pulmonary inflammation caused by silica dioxide nanoparticles in mice via TXNIP/NLRP3 signaling pathway

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Abstract

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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Acknowledgements

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education [NRF-2016R1D1A2B04936124].

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Author notes

  1. Je-Oh Lim and Je-Won Ko contributed equally to the work.

Authors and Affiliations

  1. College of Veterinary Medicine, Chonnam National University, Gwangju, 61186, Republic of Korea

    Je-Oh Lim, Tae-Yang Jung, Woong-Il Kim, So-Won Pak, In-Sik Shin & Jong-Choon Kim

  2. College of Veterinary Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea

    Je-Won Ko

  3. Laboratory Animal Resource Center, Korea Research , Institute of Bioscience and Biotechnology, Cheongju, 28116, Republic of Korea

    Won-Kee Yun & Hyoung-Chin Kim

  4. Gyeongnam Branch Institute, Bioenvironmental Science & Toxicology Division, Korea Institute of Toxicology, Jinju, 52834, Republic of Korea

    Jeong-Doo Heo

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  1. Je-Oh Lim
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Contributions

J-OL, I-SS, and J-CK designed the experimental approach and wrote the manuscript. J-WK, H-CK, and J-DH refined the experimental protocols. T-YJ, W-IK, and S-WP performed the animal experiments, biochemical analysis, and histopathological examination. Statistical analyses were done by W-KY. All authors reviewed and approved the final manuscript.

Corresponding authors

Correspondence to Jeong-Doo Heo or Jong-Choon Kim.

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Conflict of interest

Je-Oh Lim, Je-Won Ko, Tae-Yang Jung, Woong-Il Kim, So-Won Pak, In-Sik Shin, Won-Kee Yun, Hyoung-Chin Kim, Jeong-Doo Heo, and Jong-Choon Kim declare that they have no conflict of interest.

Human and animal rights

The experimental animal facility and study protocols were approved by the Institutional Animal Care and Use Committee of Chonnam National University. The animals were cared for in accordance with the Guide for the Care and Use of Laboratory Animals (NIH, 1978) and the National Animal Welfare Law of the Republic of Korea.

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Lim, JO., Ko, JW., Jung, TY. et al. Pulmonary inflammation caused by silica dioxide nanoparticles in mice via TXNIP/NLRP3 signaling pathway. Mol. Cell. Toxicol. 16, 245–252 (2020). https://doi.org/10.1007/s13273-020-00080-y

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