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

Abstract

BackgroundTumor 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.ResultsWe 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.ConclusionTNF-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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-014-0229-z) contains supplementary material, which is available to authorized users.

Mangiferin ameliorates Porphyromonas gingivalis‐induced experimental periodontitis by inhibiting phosphorylation of nuclear factor‐κB and Janus kinase 1–signal transducer and activator of transcription signaling pathways

“…In the disorder, over‐expression of proinflammatory cytokines, such as TNF‐α, can be observed in periodontal tissues . TNF‐α is released by a variety of different cells in response to various stimuli, including P. gingivalis . It can strongly amplify inflammatory responses, including inflammatory mediator production, leading to exacerbated tissue damage .…”

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“…Porphyromonas gingivalis is a Gram-negative anaerobic bacterium that is considered a keystone pathogen (4). It produces several virulence factors such as lipopolysaccharide (LPS) and fimbriae in order to activate macrophages (5,6) and invade different cell types, such as endothelial (7) and epithelial cells (8,9). Several mechanisms, such as modulation of gene and protein expression, are used by P. gingivalis to compromise immune function at the periodontal level (1,3).…”

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