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

// Isaac K. Sundar 1, Fawad Javed 2, Georgios E. Romanos 3, Irfan Rahman 1 1 Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY 2 Department of General Dentistry, Eastman Institute for Oral Health University of Rochester, Rochester, NY 3 Department of Periodontology, School of Dental Medicine, Stony Brook University, Stony Brook, NY Correspondence to: Irfan Rahman, email: irfanᵣahman@urmc. rochester. edu Keywords: e-cigarettes, e-juices, RAGE, COX 2, PGE 2 Received: August 02, 2016 Accepted: October 14, 2016 Published: October 24, 2016 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.