Thioredoxin-interacting protein as a crucial regulator in asthma exacerbation induced by copper oxide nanoparticles in a mouse model.

Copper oxide nanoparticles (CuONPs) are increasingly used across various industrial applications, raising concerns about their potential toxicity and necessitating comprehensive safety evaluations. In this study, we first evaluated the respiratory toxicity of CuONP exposure in a mouse model of asthma. CuONP exposure alone exacerbated asthma symptoms, as evidenced by increased airway hyperresponsiveness, inflammatory cell infiltration, and elevated cytokine production with increasing thioredoxin-interacting protein (TXNIP) expression. We then investigated whether TXNIP functions as a critical regulator of asthma exacerbation by examining the effects of TXNIP on the same experimental models using induced TXNIP-overexpressed mice induced by intratracheal injection of adeno-associated virus (AAV)2/8 and TXNIP knock-out (KO) mice. In CuONP-exposed asthmatic animals, TXNIP overexpressed animals significantly increased airway hyperresponsiveness, inflammatory cell counts and the production of helper type 2 cytokines, including interleukin (IL)-5 and IL-13, as well as the IL-1β, IL-6, tumor necrosis factor (TNF)-α, interferon gamma (IFN-γ) and IL-10 compared with the green fluorescent protein (GFP)-expressing controls. These responses were accompanied by the elevation of inflammatory infiltration, mucus production and the expression of apoptotic markers in lung tissues. By contrast, TXNIP KO animals markedly reduced the pathophysiological factors, inflammatory responses, mucus production and the expression of apoptotic markers in lung tissue compared with the wild-type (WT) animals. Collectively, these findings demonstrate that TXNIP plays a crucial role in regulating inflammatory responses and cell death in CuONP-exposed asthmatic mice, suggesting its potential as a therapeutic target for CuONP-induced asthma exacerbation.