NFE2L2/NRF2, OGG1, and cytokine responses of human gingival keratinocytes against oxidative insults of various origin

Kasnak G., Kononen E., Syrjanen S., Gursoy M., Zeidan-Chulia F., Firatli E., ...More

MOLECULAR AND CELLULAR BIOCHEMISTRY, vol.452, pp.63-70, 2019 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 452
  • Publication Date: 2019
  • Doi Number: 10.1007/s11010-018-3412-y
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.63-70
  • Keywords: Reactive oxygen species, Anti-oxidative response, Porphyromonas gingivalis, Lipopolysaccharide, Nicotine, 4-Nitroquinoline N-oxide, PORPHYROMONAS-GINGIVALIS, EXPRESSION, LIPOPOLYSACCHARIDE, NICOTINE, INTERLEUKIN-8, STIMULATION, ACTIVATION, SMOKING, DISEASE, IMPACT
  • Istanbul University Affiliated: Yes


ObjectiveBacterial or tobacco-related insults induce oxidative stress in gingival keratinocytes. The aim of this study was to investigate anti-oxidative and cytokine responses of human gingival keratinocytes (HMK cells) against Porphyromonas gingivalis lipopolysaccharide (Pg LPS), nicotine, and 4-nitroquinoline N-oxide (4-NQO).Materials and methodsHMK cells were incubated with Pg LPS (1 mu l/ml), nicotine (1.54mM), and 4-NQO (1 mu M) for 24h. Intracellular and extracellular levels of interleukin (IL)-1, IL-1 receptor antagonist (IL-1Ra), IL-8, monocyte chemoattractant protein (MCP)-1, and vascular endothelial growth factor (VEGF) were measured with the Luminex (R) xMAP technique, and nuclear factor, erythroid 2 like 2 (NFE2L2/NRF2) and 8-oxoguanine DNA glycosylase (OGG1) with Western blots. Data were statistically analyzed by two-way ANOVA with Bonferroni correction.ResultsAll tested oxidative stress inducers increased intracellular OGG1 levels, whereas only nicotine and 4-NQO induced NFE2L2/NRF2 levels. Nicotine, 4-NQO, and their combinational applications with Pg LPS induced the secretions of IL-1 and IL-1Ra, while that of IL-8 was inhibited by the presence of Pg LPS. MCP-1 secretion was suppressed by nicotine, alone and together with Pg LPS, while 4-NQO activated its secretion. Treatment of HMK cells with Pg LPS, nicotine, 4-NQO, or their combinations did not affect VEGF levels.ConclusionPg LPS, nicotine, and 4-NQO induce oxidative stress and regulate anti-oxidative response and cytokine expressions in human gingival keratinocytes differently. These results may indicate that bacterial and tobacco-related insults regulate distinct pathways.