Abstract | Background:
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. Objective: 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. Methods:
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. Results: 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. Conclusions: Our findings suggest that vanadium co-exposure exacerbates epithelial ROS generation that contribute to increased allergic airway inflammation and remodeling.
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Authors | Wei Tu, Xiaojun Xiao, Jiahua Lu, Xiaoyu Liu, Eryi Wang, Ruyi Yuan, Rongjun Wan, Yingchun Shen, Damo Xu, Pingchang Yang, Miao Gong, Peisong Gao, Shau-Ku Huang |
Journal | Frontiers in immunology
(Front Immunol)
Vol. 13
Pg. 1099509
( 2022)
ISSN: 1664-3224 [Electronic] Switzerland |
PMID | 36776398
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2023 Tu, Xiao, Lu, Liu, Wang, Yuan, Wan, Shen, Xu, Yang, Gong, Gao and Huang. |
Chemical References |
- Vanadium
- Reactive Oxygen Species
- Antioxidants
- Cytokines
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Topics |
- Animals
- Mice
- Humans
- Vanadium
(toxicity)
- Reactive Oxygen Species
- Airway Remodeling
- Antioxidants
(pharmacology)
- Asthma
(etiology)
- Cytokines
(metabolism)
- Inflammation
(complications)
- Pyroglyphidae
- Dermatophagoides pteronyssinus
- Oxidative Stress
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