{"doi":"10.3389/fphar.2022.1012723","title":"Vegetable glycerin e-cigarette aerosols cause airway inflammation and ion channel dysfunction","abstract":"Vegetable glycerin (VG) and propylene glycol (PG) serve as delivery vehicles for nicotine and flavorings in most e-cigarette (e-cig) liquids. Here, we investigated whether VG e-cig aerosols, in the absence of nicotine and flavors, impact parameters of mucociliary function in human volunteers, a large animal model (sheep), and air-liquid interface (ALI) cultures of primary human bronchial epithelial cells (HBECs). We found that VG-containing (VG or PG/VG), but not sole PG-containing, e-cig aerosols reduced the activity of nasal cystic fibrosis transmembrane conductance regulator (CFTR) in human volunteers who vaped for seven days. Markers of inflammation, including interleukin-6 (IL6), interleukin-8 (IL8) and matrix metalloproteinase-9 (MMP9) mRNAs, as well as MMP-9 activity and mucin 5AC (MUC5AC) expression levels, were also elevated in nasal samples from volunteers who vaped VG-containing e-liquids. In sheep, exposures to VG e-cig aerosols for five days increased mucus concentrations and MMP-9 activity in tracheal secretions and plasma levels of transforming growth factor-beta 1 (TGF-β1). In vitro exposure of HBECs to VG e-cig aerosols for five days decreased ciliary beating and increased mucus concentrations. VG e-cig aerosols also reduced CFTR function in HBECs, mechanistically by reducing membrane fluidity. Although VG e-cig aerosols did not increase MMP9 mRNA expression, expression levels of IL6, IL8, TGFB1, and MUC5AC mRNAs were significantly increased in HBECs after seven days of exposure. Thus, VG e-cig aerosols can potentially cause harm in the airway by inducing inflammation and ion channel dysfunction with consequent mucus hyperconcentration.","journal":"Frontiers in Pharmacology","year":2022,"id":241869,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":40,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9617,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":425784,"name":"Samuel Chung","orcid":"0000-0002-4988-0606","position":1,"is_corresponding":false},{"id":366798,"name":"John S. Dennis","orcid":"0000-0002-0323-2136","position":2,"is_corresponding":false},{"id":366799,"name":"Makoto Yoshida","orcid":"0000-0002-2846-2069","position":3,"is_corresponding":false},{"id":872077,"name":"Carolina Aguiar","orcid":null,"position":4,"is_corresponding":false},{"id":872078,"name":"S. Paredes Aller","orcid":null,"position":5,"is_corresponding":false},{"id":872079,"name":"Eliana S. Mendes","orcid":null,"position":6,"is_corresponding":false},{"id":354198,"name":"Andreas Schmid","orcid":"0000-0003-4054-1971","position":7,"is_corresponding":false},{"id":872080,"name":"Juan Sabater","orcid":null,"position":8,"is_corresponding":false},{"id":345669,"name":"Nathalie Baumlin","orcid":"0000-0002-5341-6785","position":9,"is_corresponding":false},{"id":345670,"name":"Matthias Salathé","orcid":"0000-0001-9092-4861","position":10,"is_corresponding":false},{"id":366795,"name":"Michael D. Kim","orcid":"0000-0003-2103-6603","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T00:23:00.865267Z","pmid":"36225570","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":[]}