title: TNF-α augmented Porphyromonas gingivalis invasion in human gingival epithelial cells through Rab5 and ICAM-1.
abstract: BACKGROUND
  Tumor necrosis factor alpha (TNF-α) plays a central role in the initiation and maintenance of immune responses to periodontopathic bacteria. However, excess TNF-α leads to dysregulated immune responses and progression of periodontitis. Porphyromonas gingivalis (P. gingivalis) invades gingival epithelial cells and then multiplies and survives for a long period. Additionally, increment of TNF-α in periodontal sites is associated with a high prevalence of gram-negative anaerobes such as P. gingivalis. However, it has not been determined whether TNF-α affects invasion of P. gingivalis in periodontal tissues.
  
  
  RESULTS
  We examined the effect of TNF-α on invasion of P. gingivalis in gingival epithelial cells and clarified the mechanism by which TNF-α augments invasion of P. gingivalis. Invasion of P. gingivalis into Ca9-22 cells was augmented by stimulation with TNF-α and it was inhibited by treatment with an antibody to TNF receptor-1. TNF-α increased production of ICAM-1, and P. gingivalis invasion was inhibited by an antibody to ICAM-1 in Ca9-22 cells. Silencing of Rab5 mRNA inhibited P. gingivalis invasion. Furthermore, the JNK inhibitor SP600125 inhibited invasion of P. gingivalis and also decreased the active form of Rab5 in Ca9-22 cells.
  
  
  CONCLUSIONS
  TNF-α augments invasion of P. gingivalis in human gingival epithelial cells through increment of ICAM-1 and activation of Rab5. These phenomena may contribute to persistent infection of P. ginigvalis and prolongation of immune responses in periodontal tissues.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Kato
authors.forename: Makoto
authors.initials: M
authors.lastname: Hagiwara
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ishihara
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Isoda
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Sugiura
authors.forename: Toshinori
authors.initials: T
authors.lastname: Komatsu
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Ishida
authors.forename: Toshihide
authors.initials: T
authors.lastname: Noguchi
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsushita
mesh_terms: D002460:Cell Line; D004705:Endocytosis; D004847:Epithelial Cells / Q000187:drug effects* / Q000382:microbiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D016966:Porphyromonas gingivalis / Q000254:growth & development / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C427755:RAB5C protein, human; D020696:rab5 GTP-Binding Proteins