Abstract
Nicotine inhalation via electronic cigarettes (e‐cigs) is an emerging concern. However, little is known about the acute toxicity in the lungs following inhalation of nicotine‐containing e‐cig aerosols. We hypothesized that acute exposure to aerosolized nicotine causes lung toxicity by eliciting inflammatory and dysregulated repair responses. Adult C57BL/6J mice were exposed 2 hours daily for 3 days to e‐cig aerosols containing propylene glycol (PG) with or without nicotine. Acute exposure to nicotine‐containing e‐cig aerosols induced inflammatory cell influx (neutrophils and CD8a+ T lymphocytes), and release of pro‐inflammatory cytokines in bronchoalveolar lavage fluid in a sex‐dependent manner. Inhalation of e‐cig aerosol containing PG alone significantly augmented the lung levels of various homeostasis/repair mediators (PPARγ, ADRP, ACTA2, CTNNB1, LEF1, β‐catenin, E‐cadherin, and MMP2) in a sex‐dependent manner when compared to air controls. These findings were accompanied by an increase in protein abundance and altered gene expression of lipogenic markers (PPARγ, ADRP) and myogenic markers (fibronectin, α‐smooth muscle actin and β‐catenin), suggesting a dysregulated repair response in mouse lungs. Furthermore, exposure to nicotine‐containing e‐cig aerosols or PG alone differentially affected the release of pro‐inflammatory cytokines in healthy and COPD human 3D EpiAirway tissues. Overall, acute exposure to nicotine‐containing e‐cig aerosols was sufficient to elicit a pro‐inflammatory response and altered mRNA and protein levels of myogenic, lipogenic, and extracellular matrix markers in mouse lung in a sex‐dependent manner. Thus, acute exposure to inhaled nicotine via e‐cig leads to dysregulated repair and inflammatory responses, which may lead to airway remodeling in the lungs.
Highlights
Electronic nicotine delivery systems (ENDS) have recently emerged as an alternative to cigarette smoking.[1,2] Electronic cigarettes (e‐cigs) are devices which use heat to aerosolize a small amount of e‐liquid containing nicotine solubilized in propylene glycol (PG) or vegetable glycerin (VG) as a base constituent, humectant.[3,4] e‐cig use, or “vaping,” is perceived as safer than smoking conventional tobacco cigarettes,[5,6,7] very little is known about the systemic and pulmonary consequences of acute and chronic e‐cig exposure in vivo
To the best of our knowledge, no study has yet evaluated the differential effects of inhaled aerosols containing PG with and without nicotine on lung inflammation and dysregulated repair responses in a sex‐dependent manner
After 3 days of e‐cig exposure in male mice, Glynos et al[25] reported increased total cell count and macrophages, and even higher cellular influx than seen with cigarette smoke exposure. The differences in these results could be due to several reasons including, but not limited to differences in the method of e‐cig exposure, the mouse strain and sexes used, the types of e‐liquids, the concentration of nicotine, and the vendor/commercial sources of e‐liquids used in these studies
Summary
Electronic nicotine delivery systems (ENDS) have recently emerged as an alternative to cigarette smoking.[1,2] Electronic cigarettes (e‐cigs) are devices which use heat to aerosolize a small amount of e‐liquid containing nicotine (up to 24‐100 mg/ mL) solubilized in propylene glycol (PG) or vegetable glycerin (VG) as a base constituent, humectant.[3,4] e‐cig use, or “vaping,” is perceived as safer than smoking conventional tobacco cigarettes,[5,6,7] very little is known about the systemic and pulmonary consequences of acute and chronic e‐cig exposure in vivo. C57BL/6J mice to e‐cig aerosols containing PG with and without nicotine using an e‐cig device in order to determine the mechanism underlying the lung pathophysiological consequences (inflammatory and dysregulated repair markers) in our acute model of inhaled nicotine exposure. The inflammatory response to aerosolized nicotine was examined using an in vitro human 3D EpiAirwayTM model/system
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