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

Oncotarget. 2016 Nov 22;7(47):77196-77204. doi: 10.18632/oncotarget.12857.

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.

Keywords: COX2; PGE2; RAGE; e-cigarettes; e-juices.

MeSH terms

  • Cells, Cultured
  • Cellular Senescence
  • Cytokines / metabolism
  • DNA Damage
  • Electronic Nicotine Delivery Systems
  • Epithelial Cells / cytology
  • Epithelial Cells / immunology
  • Fibroblasts / cytology
  • Fibroblasts / immunology
  • Flavoring Agents / adverse effects*
  • Gingiva / cytology*
  • Gingiva / immunology
  • Glycation End Products, Advanced / metabolism
  • Histone Deacetylase 2 / metabolism
  • Humans
  • Inflammation / chemically induced*
  • Inflammation / metabolism
  • Mouth / cytology*
  • Oxidative Stress
  • Periodontal Ligament / cytology*
  • Periodontal Ligament / immunology

Substances

  • Cytokines
  • Flavoring Agents
  • Glycation End Products, Advanced
  • HDAC2 protein, human
  • Histone Deacetylase 2