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Titanium Dioxide Nanoparticles Exacerbate Allergic Airway Inflammation via TXNIP Upregulation in a Mouse Model of Asthma

1
College of Veterinary Medicine (BK21 FOUR Program), Chonnam National University, Gwangju 61186, Korea
2
Bioenvironmental Science & Technology Division, Korea Institute of Toxicology, Jinju 52834, Korea
3
College of Veterinary Medicine, Chungnam National University, Daejeon 34131, Korea
*
Authors to whom correspondence should be addressed.
Academic Editors: Kalevi Kairemo and Daniela Montesarchio
Int. J. Mol. Sci. 2021, 22(18), 9924; https://doi.org/10.3390/ijms22189924
Received: 9 August 2021 / Revised: 8 September 2021 / Accepted: 10 September 2021 / Published: 14 September 2021
(This article belongs to the Section Biochemistry)
Titanium dioxide nanoparticles (TiO2NPs) are widely used in industrial and medicinal fields and in various consumer products, and their increasing use has led to an increase in the number of toxicity studies; however, studies investigating the underlying toxicity mechanism have been rare. In this study, we evaluated potential toxic effects of TiO2NPs exposure on lungs as well as the development of asthma through the ovalbumin (OVA)-induced mouse model of asthma. Furthermore, we also investigated the associated toxic mechanism. TiO2NPs caused pulmonary toxicity by exacerbating the inflammatory response, indicated by an increase in the number and level of inflammatory cells and mediators, respectively. OVA-induced asthma exposed mice to TiO2NPs led to significant increases in inflammatory mediators, cytokines, and airway hyperresponsiveness compared with those in non-exposed asthmatic mice. This was also accompanied by increased inflammatory cell infiltration and mucus production in the lung tissues. Additionally, TiO2NPs decreased the expression of B-cell lymphoma 2 (Bcl2) and the expressions of thioredoxin-interacting protein (TXNIP), phospho-apoptosis signal-regulating kinase 1, Bcl2-associated X, and cleaved-caspase 3 were escalated in the lungs of asthmatic mice compared with those in non-exposed asthmatic mice. These responses were consistent with in vitro results obtained using human airway epithelial cells. TiO2NPs treated cells exhibited an increase in the mRNA and protein expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α with an elevation of TXNIP signaling compared to non-treated cells. Moreover, pathophysiological changes induced by TiO2NP treatment were significantly decreased by TXNIP knockdown in airway epithelial cells. Overall, TiO2NP exposure induced toxicological changes in the respiratory tract and exacerbated the development of asthma via activation of the TXNIP-apoptosis pathway. These results provide insights into the underlying mechanism of TiO2NP-mediated respiratory toxicity. View Full-Text
Keywords: titanium dioxide nanoparticle; asthma; airway inflammation; thioredoxin-interacting protein; apoptosis titanium dioxide nanoparticle; asthma; airway inflammation; thioredoxin-interacting protein; apoptosis
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MDPI and ACS Style

Lim, J.-O.; Lee, S.-J.; Kim, W.-I.; Pak, S.-W.; Moon, C.; Shin, I.-S.; Heo, J.-D.; Ko, J.-W.; Kim, J.-C. Titanium Dioxide Nanoparticles Exacerbate Allergic Airway Inflammation via TXNIP Upregulation in a Mouse Model of Asthma. Int. J. Mol. Sci. 2021, 22, 9924. https://doi.org/10.3390/ijms22189924

AMA Style

Lim J-O, Lee S-J, Kim W-I, Pak S-W, Moon C, Shin I-S, Heo J-D, Ko J-W, Kim J-C. Titanium Dioxide Nanoparticles Exacerbate Allergic Airway Inflammation via TXNIP Upregulation in a Mouse Model of Asthma. International Journal of Molecular Sciences. 2021; 22(18):9924. https://doi.org/10.3390/ijms22189924

Chicago/Turabian Style

Lim, Je-Oh, Se-Jin Lee, Woong-Il Kim, So-Won Pak, Changjong Moon, In-Sik Shin, Jeong-Doo Heo, Je-Won Ko, and Jong-Choon Kim. 2021. "Titanium Dioxide Nanoparticles Exacerbate Allergic Airway Inflammation via TXNIP Upregulation in a Mouse Model of Asthma" International Journal of Molecular Sciences 22, no. 18: 9924. https://doi.org/10.3390/ijms22189924

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