E-cigarettes and flavorings induce inflammatory and pro-senescence responses in oral epithelial cells and periodontal fibroblasts

Abstract

Electronic-cigarettes (e-cigs) represent a significant and increasing proportion of tobacco product consumption, which may pose an oral health concern. Oxidative/carbonyl stress via protein carbonylation is an important factor in causing inflammation and DNA damage. This results in stress-induced premature senescence (a state of irreversible growth arrest which re-enforces chronic inflammation) in gingival epithelium, which may contribute to the pathogenesis of oral diseases. We show that e-cigs with flavorings cause increased oxidative/carbonyl stress and inflammatory cytokine release in human periodontal ligament fibroblasts, Human Gingival Epithelium Progenitors pooled (HGEPp), and epigingival 3D epithelium. We further show increased levels of prostaglandin-E2 and cycloxygenase-2 are associated with upregulation of the receptor for advanced glycation end products (RAGE) by e-cig exposure-mediated carbonyl stress in gingival epithelium/tissue. Further, e-cigs cause increased oxidative/carbonyl and inflammatory responses, and DNA damage along with histone deacetylase 2 (HDAC2) reduction via RAGE-dependent mechanisms in gingival epithelium. A greater response is elicited by flavored e-cigs. Increased oxidative stress, pro-inflammatory and pro-senescence responses (DNA damage and HDAC2 reduction) can result in dysregulated repair due to proinflammatory and pro-senescence responses in periodontal cells. These data highlight the pathologic role of e-cig aerosol and its flavoring to cells and tissues of the oral cavity in compromised oral health.

Proinflammatory cytokine levels and peri‐implant parameters among cigarette smokers, individuals vaping electronic cigarettes, and non‐smokers

“…Recent findings on vaping e‐cigs and clinical/radiographic periodontal outcomes indicates that individuals vaping e‐cigs showed significantly higher probing depths, poor attachment loss, and increased marginal bone loss as compared with nonsmokers ; however, to the authors’ knowledge, the present study is the first study to compare clinical and radiographic status around dental implants and proinflammatory cytokine levels among CS, vaping individuals, and nonsmokers. The present study supports the hypothesis that peri‐implant clinical and radiographic parameters are worse and the levels of proinflammatory cytokine are higher among CS and individuals vaping e‐cigs when compared with individuals who have never consumed tobacco in any form.…”

“…From the dental health perspective, vaping has been associated with several oral disorders including submucous fibrosis and periodontal diseases . A laboratory investigation by Sundar et al . reported that e‐cig aerosols with flavoring agents may have a negative impact on oral epithelial cells and gingival fibroblasts through DNA damage and elevated expression of proinflammatory cytokines such as cyclooxygenase (COX)‐2 and prostaglandin E2 (PGE 2 ).…”

Comparison of Periodontal Parameters and Self‐Perceived Oral Symptoms Among Cigarette Smokers, Individuals Vaping Electronic Cigarettes, and Never‐Smokers

“…This result is in accordance with a recent study 27 in which vaping individuals considered e‐cigs as non‐hazardous and more beneficial than smoking cigarettes. From a clinical perspective, there are no studies that have shown vaping e‐cigs to have detrimental effects on periodontal health status; however, a recent in vitro study 1 showed that exposure of human PDL fibroblast and gingival epithelial cells to e‐cig vapor with flavorings increased oxidative stress and DNA damage and enhanced release of proinflammatory cytokines (PGE2 and COX‐2). In this regard, it is premature to label vaping as safe.…”

“…Electronic cigarettes (e‐cigs) are battery‐operated handheld devices in which an e‐liquid (containing nicotine and sometimes artificial flavors such as menthol, coffee, candy, butter, and fruits) is heated by a heating element releasing a chemical‐filled aerosol for inhalation 1 . In the United States, use of e‐cigs is escalating, predominantly in younger adults 2 .…”

“…From an oral health perspective, vaping has been implicated in oral diseases, such as oral submucous fibrosis and periodontal diseases 8,9 . In vitro results by Sundar et al 1 demonstrated that exposure of oral epithelial cells and periodontal ligament (PDL) fibroblasts to e‐cig vapor/aerosol with flavorings increased DNA damage and enhanced expression of proinflammatory cytokines such as cycloxygenase (COX))‐2 and prostaglandin E2 (PGE2) in these cells. Moreover, it has also been reported that e‐cig vaping induces oxidative stress and increases expression of advanced glycation end products (AGEs) and their receptors in oral epithelial cells, including gingival tissues 1 .…”