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

E-cigarettes and flavorings induce inflammatory and pro-senescence responses in oral epithelial cells and periodontal fibroblasts.
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DOI:
10.18632/oncotarget.12857
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发表时间:
2016-11-22
期刊:
影响因子:
--
通讯作者:
Rahman I
Rahman I
中科院分区:
其他
文献类型:
--
作者:
Sundar IK;Javed F;Romanos GE;Rahman I

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电子烟(e-cigs)在烟草产品消费中占很大比例,而且比例越来越高,这可能会对口腔健康造成影响。通过蛋白质甲基化造成的氧化/羰基应激是引起炎症和DNA损伤的重要因素。这会导致应激诱导的牙龈上皮过早衰老(一种不可逆转的生长停滞状态,从而重新加剧慢性炎症),这可能有助于口腔疾病的发病。我们发现,含有调味料的电子烟可导致人牙周膜成纤维细胞、人牙龈上皮祖细胞池(HGEPp)和牙周膜3D上皮细胞氧化/羰基应激和炎性细胞因子释放增加。我们进一步表明,前列腺素E2和环氧合酶-2水平的增加与电子烟暴露介导的牙龈上皮/组织中的羰基应激上调晚期糖基化终产物受体(RAGE)有关。此外,E-CIG通过RAGE依赖的机制导致牙龈上皮细胞氧化/羰基和炎症反应增加,DNA损伤和组蛋白脱乙酰基酶2(HDAC2)减少。调味的电子烟引起了更大的反响。氧化应激、促炎和促衰老反应的增加(DNA损伤和HDAC2减少)可导致牙周细胞的促炎和促衰老反应而导致失调的修复。这些数据突出了e-cig气雾剂及其对口腔细胞和组织的调味在损害口腔健康方面的病理作用。
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.