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

Abstract

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.

Upcycling discarded cellulosic surgical masks into catalytically active freestanding materials

“…However, some adverse cytotoxic effects have been reported for cobalt oxide, which can release Co ions that can result in generating oxidative stress (Cavallo et al 2015 ). The biocompatibility of used metal oxide nanoparticles coupled with the innocuous character of cellulose makes these materials interesting for biomedical applications, although special care should be paid to the possible allergic reactions against human skin (Larsen et al 2010 ; Cho et al 2012 ; Horie et al 2015 ; Ngobili and Daniele 2016 ; Lim et al 2021 ).…”

Inner Shell of the Chestnut (Castanea crenatta) Suppresses Inflammatory Responses in Ovalbumin-Induced Allergic Asthma Mouse Model

“…Following blood collection, BALF was collected from the mice and processed as previously described [ 19 ]. Briefly, after the tracheotomy, an endotracheal syringe was intubated into the trachea.…”

Thioredoxin-1: A Promising Target for the Treatment of Allergic Diseases

“…Trx1 and Txnip are normally combined into a dimer, and the Trx1/Txnip dimer is separated in the presence of irritant factors such as inflammation. Txnip can activate such signaling pathways as ASK1, Bax, p38, and Caspase3, and induce apoptosis in the lung tissue ( 33 ). Moreover, Txnip can also activate inflammasomes to trigger inflammatory reactions ( 33 ), all of which aggravate the symptoms of allergic asthma.…”

“…Txnip can activate such signaling pathways as ASK1, Bax, p38, and Caspase3, and induce apoptosis in the lung tissue ( 33 ). Moreover, Txnip can also activate inflammasomes to trigger inflammatory reactions ( 33 ), all of which aggravate the symptoms of allergic asthma. Trx1, on the other hand, inhibits these reactions, thereby maintaining the balance between Trx and Txnip.…”