Vanadium exposure exacerbates allergic airway inflammation and remodeling through triggering reactive oxidative...

Metal components of environmental PM2.5 are associated with the exacerbation of allergic diseases like asthma. In our recent hospital-based population study, exposure to vanadium is shown to pose a significant risk for current asthma, but the causal relationship and its underlying molecular mechanisms remain unclear.

We sought to determine whether vanadium co-exposure can aggravate house dust mite (HDM)-induced allergic airway inflammation and remodeling, as well as investigate its related mechanisms.

Asthma mouse model was generated by using either vanadium pentoxide (V₂O₅) or HDM alone or in combination, in which the airway inflammation and remodeling was investigated. The effect of V₂O₅ co-exposure on HDM-induced epithelial-derived cytokine release and oxidative stress (ROS) generation was also examined by in vitro analyses. The role of ROS in V₂O₅ co-exposure-induced cytokine release and airway inflammation and remodeling was examined by using inhibitors or antioxidant.

Compared to HDM alone, V₂O₅ co-exposure exacerbated HDM-induced airway inflammation with increased infiltration of inflammatory cells and elevated levels of Th1/Th2/Th17 and epithelial-derived (IL-25, TSLP) cytokines in the bronchoalveolar lavage fluids (BALFs). Intriguingly, V₂O₅ co-exposure also potentiated HDM-induced airway remodeling. Increased cytokine release was further supported by in vitro analysis in human bronchial epithelial cells (HBECs). Mechanistically, ROS, particularly mitochondrial-derived ROS, was significantly enhanced in HBECs after V₂O₅ co-exposure as compared to HDM challenge alone. Inhibition of ROS with its inhibitor N-acetyl-L-cysteine (NAC) and mitochondrial-targeted antioxidant MitoTEMPO blocked the increased epithelial release caused by V₂O₅ co-exposure. Furthermore, vitamin D₃ as an antioxidant was found to inhibit V₂O₅ co-exposure-induced increased airway epithelial cytokine release and airway remodeling.

Our findings suggest that vanadium co-exposure exacerbates epithelial ROS generation that contribute to increased allergic airway inflammation and remodeling.