Pathophysiological Responses of Oral Keratinocytes After Exposure to Flavored E-Cigarette Liquids

Electronic cigarettes (ECIGs) have grown in popularity, particularly among adolescents and young adults. Flavored ECIG-liquids (E-liquids) are aerosolized by these ECIGs and inhaled into the respiratory system. Several studies have shown detrimental effects of E-liquids in airway tissues, revealing that flavoring agents may be the most irritating component. However, research on the effects of E-liquids on biological processes of the oral cavity, which is the first site of aerosol contact, is limited. Hence, this study focuses on the effects of E-liquid flavors on oral epithelial cells using the OKF6/TERT-2 cell line model.

E-liquid was prepared with and without flavors (tobacco, menthol, cinnamon, and strawberry). OKF6/TERT-2 oral epithelial cells, cultured at 37 °C and 5% CO₂, were exposed to 1% E-liquid ± flavors for 24 h. Outcomes determined include cell morphology, media pH, wound healing capability, oxidative stress, expression of mucin and tight junction genes, glycoprotein release, and levels of inflammatory cytokines (TNFα, IL-6, and IL-8).

Exposure to 1% flavored E-liquids negatively affect cellular confluency, adherence, and morphology. E-liquids ± flavors, particularly cinnamon, increase oxidative stress and production of IL-8, curtail wound healing recovery, and decrease glycoprotein release. Gene expression of muc5b is downregulated after exposure to E-liquids. In contrast, E-liquids upregulate occludin and claudin-1.

This study suggests that ECIG use is not without risk. Flavored E-liquids, particularly cinnamon, result in pathophysiological responses of OKF6/TERT-2 cells. The dysregulation of inflammatory responses and cellular biology induced by E-liquids may contribute to various oral pathologies.