Transcriptomic Response of Primary Human Bronchial Cells to Repeated Exposures of Cigarette and ENDS Preparations

Cigarette smoke deregulates several biological pathways by modulating gene expression in airway epithelial cells and altering the physiology of the airway epithelium. The effects of repeated exposures of electronic cigarette delivery systems (ENDS) on gene expression in airway epithelium are relatively unknown. In order to assess the effect of repeated exposures of ENDS, primary normal human bronchial epithelial (NHBE) cells grown at air-liquid interface (ALI) were exposed to cigarette and ENDS preparations daily for 10 days. Cigarette smoke preparations significantly altered gene expression in a dose-dependent manner compared to vehicle control, including genes linked to oxidative stress, xenobiotic metabolism, cancer pathways, epithelial-mesenchymal transition, fatty acid metabolism, degradation of collagen and extracellular matrix, O-glycosylation, and chemokines/cytokines, which are known pathways found to be altered in smokers. Conversely, ENDS preparations had minimal effect on transcriptional pathways. This study revealed that a sub-chronic exposure of primary NHBE cultures to cigarette and ENDS preparations differentially regulated genes and canonical pathways, with minimal effect observed with ENDS preparations compared to cigarette preparations. This study also demonstrates the versatility of primary NHBE cultures at ALI to evaluate repeat-dose exposures of tobacco products.