{"doi":"10.3389/fimmu.2022.1099509","title":"Vanadium exposure exacerbates allergic airway inflammation and remodeling through triggering reactive oxidative stress","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 (V 2 O 5 ) or HDM alone or in combination, in which the airway inflammation and remodeling was investigated. The effect of V 2 O 5 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 V 2 O 5 co-exposure-induced cytokine release and airway inflammation and remodeling was examined by using inhibitors or antioxidant. Results Compared to HDM alone, V 2 O 5 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, V 2 O 5 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 V 2 O 5 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 V 2 O 5 co-exposure. Furthermore, vitamin D 3 as an antioxidant was found to inhibit V 2 O 5 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.","journal":"Frontiers in Immunology","year":2023,"id":325664,"datarank":1.1236762569324683,"base_score":3.4339872044851463,"endowment":3.4339872044851463,"self_citation_contribution":0.515098080672772,"citation_network_contribution":0.6085781762596965,"self_endowment_contribution":0.515098080672772,"citer_contribution":0.6085781762596965,"corpus_percentile":null,"corpus_rank":null,"citation_count":30,"citer_count":29,"citers_with_citation_signal":23,"citers_with_endowment":23,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9632,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":699784,"name":"Xiaojun Xiao","orcid":"0000-0002-1195-0541","position":1,"is_corresponding":false},{"id":1023818,"name":"Jiahua Lu","orcid":"0000-0001-8544-891X","position":2,"is_corresponding":false},{"id":1043928,"name":"Xiaoyu Liu","orcid":"0000-0003-0078-2199","position":3,"is_corresponding":false},{"id":1044584,"name":"Eryi Wang","orcid":null,"position":4,"is_corresponding":false},{"id":1044585,"name":"Ruyi Yuan","orcid":null,"position":5,"is_corresponding":false},{"id":901702,"name":"Rongjun Wan","orcid":"0000-0003-2643-3173","position":6,"is_corresponding":false},{"id":666097,"name":"Ying‐Chun Shen","orcid":"0000-0001-8426-9071","position":7,"is_corresponding":false},{"id":1043929,"name":"Damo Xu","orcid":"0000-0003-1192-9213","position":8,"is_corresponding":false},{"id":1044586,"name":"Ping-Chang Yang","orcid":null,"position":9,"is_corresponding":false},{"id":773403,"name":"Miao Gong","orcid":null,"position":10,"is_corresponding":false},{"id":242478,"name":"Peisong Gao","orcid":"0000-0002-7651-1339","position":11,"is_corresponding":false},{"id":458134,"name":"Shau‐Ku Huang","orcid":null,"position":12,"is_corresponding":false},{"id":1016478,"name":"Wei Tu","orcid":"0000-0002-0255-4037","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:08:28.266998Z","pmid":"36776398","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}