TNF-α augmented Porphyromonas gingivalis invasion in human gingival epithelial cells through Rab5 and ICAM-1 (Epidemiologic Perspectives & Innovations)

Background: 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. Results: 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. Conclusion: 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.