TNF-α augmented Porphyromonas gingivalis invasion in human gingival epithelial cells through Rab5 and ICAM-1
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
BMC Microbiology 2014, 14:229 doi:10.1186/s12866-014-0229-zPublished: 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.