title: 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.
authors: Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY, USA.
authors: Isaac K
authors: IK
authors: Sundar
authors: Department of General Dentistry, Eastman Institute for Oral Health University of Rochester, Rochester, NY, USA.
authors: Fawad
authors: F
authors: Javed
authors: Department of Periodontology, School of Dental Medicine, Stony Brook University, Stony Brook, NY, USA.
authors: Georgios E
authors: GE
authors: Romanos
authors: Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY, USA.
authors: Irfan
authors: I
authors: Rahman
mesh_terms: D002478:Cells, Cultured; D016922:Cellular Senescence; D016207:Cytokines / Q000378:metabolism; D004249:DNA Damage; D066300:Electronic Nicotine Delivery Systems; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology; D005421:Flavoring Agents / Q000009:adverse effects*; D005881:Gingiva / Q000166:cytology* / Q000276:immunology; D017127:Glycation End Products, Advanced / Q000378:metabolism; D056464:Histone Deacetylase 2 / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism; D009055:Mouth / Q000166:cytology*; D018384:Oxidative Stress; D010513:Periodontal Ligament / Q000166:cytology* / Q000276:immunology
chemical_list: D016207:Cytokines; D005421:Flavoring Agents; D017127:Glycation End Products, Advanced; C533423:HDAC2 protein, human; D056464:Histone Deacetylase 2
keywords: COX2; PGE2; RAGE; e-cigarettes; e-juices