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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

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.

Conclusion

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.

Keywords:
Porphyromonas gingivalis; Endocytosis; TNF-α; Rab5; ICAM-1; Persistent infection