E-cigarette vapor extract alters human eosinophil gene expression in an effect mediated by propylene glycol, glycerin, and nicotine.

Abstract

E-cigarette use has become widespread, and its effects on airway inflammation and disease are not fully delineated. E-cigarette vapor extract (EVE) profoundly affects neutrophil function. We hypothesized that EVE also alters eosinophil function and thus could impact allergic airway disease. We employed RNA sequencing to measure the ex vivo effect of EVE components on human eosinophil transcription. Blood eosinophils from 9 nonvaping subjects without asthma were isolated by negative selection. Cells were incubated for 48 h with EVE consisting of glycerin, propylene glycol, and nicotine (EVE+), EVE without nicotine ("EVE-"), air-exposed media termed extract buffer (EB), or untreated media. Bulk RNA sequencing was performed. Transcriptomic analysis revealed that the EB, EVE-, and EVE+ conditions showed highly variable gene expression with respect to no treatment and each other. Differential gene expression analysis comparing a combination of EVE+, EVE-, and EB revealed 3,030 differentially expressed genes (DEGs) with an adjusted P value <0.05 and log2 fold change >0.5 or <0.5. There were 645 DEGs between EB and EVE-, 1,713 between EB and EVE+, and 404 between EVE- and EVE+. Gene set enrichment analysis demonstrated that DEGs between both EVE+ and EVE- and the EB control were positively enriched for heme metabolism and apoptosis and negatively enriched tumor necrosis factor α signaling, interferon γ signaling, and inflammatory response. Thus, EVE significantly alters eosinophil metabolic and inflammatory pathways, mediated by propylene glycol and glycerin, with both enhancing and unique effects of nicotine. This study motivates further research into the pathogenic effects of vaping on airway eosinophils and allergic airways disease.