Open Access Research article

TNF-α augmented Porphyromonas gingivalis invasion in human gingival epithelial cells through Rab5 and ICAM-1

Yoshiko Kato12, Makoto Hagiwara1, Yuichi Ishihara2, Ryutaro Isoda1, Shinsuke Sugiura2, Toshinori Komatsu1, Naoyuki Ishida12, Toshihide Noguchi2 and Kenji Matsushita1*

Author Affiliations

1 Department of Oral Disease Research, National Center of Geriatrics and Gerontology, Obu 747-8511, Aichi, Japan

2 Department of Periodontology, Aichigakuin University, Nagoya, Aichi, Japan

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BMC Microbiology 2014, 14:229  doi:10.1186/s12866-014-0229-z

Published: 3 September 2014



Tumor necrosis factor alpha (TNF-?) plays a central role in the initiation and maintenance of immune responses to periodontopathic bacteria. However, excess TNF-? 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-? 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-? affects invasion of P. gingivalis in periodontal tissues.


We examined the effect of TNF-? on invasion of P. gingivalis in gingival epithelial cells and clarified the mechanism by which TNF-? augments invasion of P. gingivalis. Invasion of P. gingivalis into Ca9-22 cells was augmented by stimulation with TNF-? and it was inhibited by treatment with an antibody to TNF receptor-1. TNF-? 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.


TNF-? 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.

Porphyromonas gingivalis; Endocytosis; TNF-?; Rab5; ICAM-1; Persistent infection