title: High glucose-induced oxidative stress increases IL-8 production in human gingival epithelial cells.
abstract: OBJECTIVE
  Diabetes is often associated with increased prevalence and severity of periodontal disease. We hypothesized that gingival epithelial cells modify periodontal disease progression and predicted that hyperglycemia would activate an inflammatory response in human gingival epithelial cells (HGECs).
  
  
  METHODS
  We tested our hypothesis in immortalized HGECs (epi 4 cells) isolated from periodontal tissue and transfected with the simian virus 40 T antigen. The epi 4 cells were cultured in high (25 mM, HG) and normal (6 mM, NG) glucose conditions.
  
  
  RESULTS
  The epi 4 cells showed increased interleukin-8 (IL-8) protein secretion and mRNA expression when cultured in HG, compared with in NG. These effects were not associated with increased cell proliferation and were not observed in a hyperosmolar control group (normal glucose with 19 mM mannitol). Increased IL-8 secretion in HG was inhibited by pretreatment with an antioxidant, N-acetylcysteine, or a protein kinase C inhibitor, Ro31-8220. Hyperglycemia did not affect IL-8 secretion by gingival fibroblasts or periodontal ligament cells. In epi 4 cells, hyperglycemia also induced expression of toll-like receptor 2 (TLR2) but not TLR4.
  
  
  CONCLUSIONS
  These findings suggest a potential participation of epithelial cells in periodontal disease during diabetes by evoking an excessive host inflammatory response.
authors.affiliation: Division of Oral Biology and Disease Control, Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kashiwagi
authors.affiliation: Division of Oral Biology and Disease Control, Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Takedachi
authors.affiliation: Division of Oral Biology and Disease Control, Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Mori
authors.affiliation: Division of Oral Biology and Disease Control, Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kubota
authors.affiliation: Division of Oral Biology and Disease Control, Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Division of Oral Biology and Disease Control, Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kitamura
authors.affiliation: Division of Oral Biology and Disease Control, Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Murakami
mesh_terms: D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000378:metabolism; D004847:Epithelial Cells / Q000502:physiology*; D005881:Gingiva / Q000166:cytology*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D018384:Oxidative Stress / Q000502:physiology*
chemical_list: D016209:Interleukin-8
keywords: high glucose; human gingival epithelial cell; interleukin-8; oxidative stress; toll-like receptor 2 (TLR2)