title: Azithromycin may inhibit interleukin-8 through suppression of Rac1 and a nuclear factor-kappa B pathway in KB cells stimulated with lipopolysaccharide.
abstract: BACKGROUND
  Recent studies have shown that the 15-member macrolide antibiotic azithromycin (AZM) not only has antibacterial activity, but also results in the role of immunomodulator. Interleukin (IL)-8 is an important inflammatory mediator in periodontal disease. However, there have been no reports on the effects of AZM on IL-8 production from human oral epithelium. Therefore, we investigated the effects of AZM on IL-8 production in an oral epithelial cell line.
  
  
  METHODS
  KB cells were stimulated by Escherichia coli or Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) lipopolysaccharide (LPS) with or without AZM. IL-8 mRNA and protein expression and production in response to LPS were analyzed by quantitative polymerase chain reaction, flow cytometry, and enzyme-linked immunosorbent assay. The activation of nuclear factor-kappa B (NF-κB) and Rac1, which is important for IL-8 expression, was analyzed by enzyme-linked immunosorbent assay and Western blotting, respectively.
  
  
  RESULTS
  IL-8 mRNA expression, IL-8 production, and NF-κB activation in LPS-stimulated KB cells were inhibited by the addition of AZM. LPS-induced Rac1 activation was also suppressed by AZM.
  
  
  CONCLUSIONS
  This study suggests that AZM inhibits LPS-induced IL-8 production in an oral epithelial cell line, in part caused by the suppression of Rac1 and NF-κB activation. The use of AZM might provide possible benefits in periodontal therapy, with respect to both its antibacterial action and apparent anti-inflammatory effect.
authors.affiliation: Department of Periodontology, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Matsumura
authors.forename: Akio
authors.initials: A
authors.lastname: Mitani
authors.forename: Takayuki
authors.initials: T
authors.lastname: Suga
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kamiya
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Shigehisa
authors.initials: S
authors.lastname: Tanaka
authors.forename: Makoto
authors.initials: M
authors.lastname: Aino
authors.forename: Toshihide
authors.initials: T
authors.lastname: Noguchi
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D020830:rac1 GTP-Binding Protein / Q000187:drug effects / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; C107953:RAC1 protein, human; D017963:Azithromycin; D020830:rac1 GTP-Binding Protein