title: Azithromycin recovers reductions in barrier function in human gingival epithelial cells stimulated with tumor necrosis factor-α.
abstract: OBJECTIVE
  The gingival epithelium plays an important role in protecting against the invasion of periodontal pathogens, and the permeability of gingival epithelial cells has been implicated in the initiation of periodontitis. Azithromycin (AZM) has been used in the treatment of chronic inflammatory airway diseases because it regulates cell-cell contact in airway epithelial cells. Therefore, AZM may also regulate barrier function in gingival epithelial cells. In the present study, we examined the effects of AZM on the permeability of human gingival epithelial cells (HGEC) under inflammatory conditions in vitro.
  
  
  METHODS
  HGEC were stimulated by tumor necrosis factor-α (TNF-α) in the presence of AZM or p38 MAP kinase and ERK inhibitors. Permeability was assessed based on transepithelial electrical resistance (TER). The expression of E-cadherin, phosphorylated p38 MAP kinase, and ERK was analyzed by Western blotting.
  
  
  RESULTS
  TNF-α decreased TER in HGEC, and AZM and the p38 MAP kinase and ERK inhibitors recovered this decrease. AZM inhibited the phosphorylation of ERK and p38 MAP kinase in TNF-α-stimulated HGEC. Furthermore, AZM recovered the decrease in E-cadherin expression in HGEC stimulated with TNF-α.
  
  
  CONCLUSIONS
  These results suggested that AZM regulated gingival epithelial permeability through p38 MAP kinase and ERK signaling, and may contribute to suppress the inflammation in gingival tissue.
authors.affiliation: Department of Periodontal Medicine, Division of Applied Life Science, Institute of Biomedical & Health Sciences, Hiroshima University, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyagawa
authors.affiliation: Department of Periodontal Medicine, Division of Applied Life Science, Institute of Biomedical & Health Sciences, Hiroshima University, Japan. Electronic address: tfuji@hiroshima-u.ac.jp.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Fujita
authors.affiliation: Department of Conservative Dentistry, Institute of Biomedical Sciences, Tokushima University Graduate School, Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Yumoto
authors.affiliation: Department of Periodontal Medicine, Division of Applied Life Science, Institute of Biomedical & Health Sciences, Hiroshima University, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yoshimoto
authors.affiliation: Department of Periodontal Medicine, Division of Applied Life Science, Institute of Biomedical & Health Sciences, Hiroshima University, Japan.
authors.forename: Mikihito
authors.initials: M
authors.lastname: Kajiya
authors.affiliation: Department of Periodontal Medicine, Division of Applied Life Science, Institute of Biomedical & Health Sciences, Hiroshima University, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Ouhara
authors.affiliation: Department of Periodontal Medicine, Division of Applied Life Science, Institute of Biomedical & Health Sciences, Hiroshima University, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Matsuda
authors.affiliation: Department of Periodontal Medicine, Division of Applied Life Science, Institute of Biomedical & Health Sciences, Hiroshima University, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Shiba
authors.affiliation: Department of Conservative Dentistry, Institute of Biomedical Sciences, Tokushima University Graduate School, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsuo
authors.affiliation: Department of Periodontal Medicine, Division of Applied Life Science, Institute of Biomedical & Health Sciences, Hiroshima University, Japan.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Kurihara
mesh_terms: D017963:Azithromycin / Q000494:pharmacology*; D015820:Cadherins / Q000378:metabolism; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005881:Gingiva / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005891:Gingivitis / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D015820:Cadherins; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D017963:Azithromycin; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Azithromycin; ERK; Human gingival epithelial cells; Permeability; p38 MAP kinase