ation with TNF. Therefore, we think that the apoptotic activity of TNF towards host cells does not affect P. gingivalis invasion. ICAM 1 as well as Rab5 was associated with TNF augmented P. gingivalis invasion. Ad hesion of P. gingivalis to host cells is multimodal and involves kinase inhibitor Bortezomib the interaction of bacterial cell surface adhesins with receptors e pressed on the surfaces of epithelial cells. Adhesion of P. gingivalis to host cells is mediated by many e tracellular components, including fimbriae, proteases, hemagglutinins, and lipopolysaccharides. Among the large array of virulence factors produced by P. gingivalis, the major fimbriae, as well as cysteine proteinases, contribute to the attachment to and invasion of oral epithelial cells. On the other hand, integrins can act as receptors for the integrin binding proteins of several bacterial species.

P. gingivalis also associates with B1 and 5B1 integrin het erodimers via FimA. VB3 integrin also mediates fimbriae adhesion to epithelial cells. In addition, carbohydrate chains on epithelial cell membrane glycolipids have been reported to act as receptors for P. gingivalis. It has been demonstrated that ICAM 1 is required for the inva sion of P. gingivalis into human oral epithelial cells. Various cytokines including TNF induce e pression of ICAM 1. Therefore, ICAM 1 e presion and P. gin givalis invasion in periodontal sites may be associated with the primary stages of the development and progression of chronic periodontitis. It has been demonstrated that a large number of intra cellular bacteria are present in IL 6 treated cells that have an increasing amount of Rab5.

These results indicate that overe pression of Rab5 by cytokines may promote the fusion of bacteria containing phagosomes with early endosomes and thereby inhibit their transport to lysosomes and may help in prolongation of bacterial survival in host cells and thus establish a chronic infection that could e acerbate the immune response. At periodon tal sites, such phenomena could occur. Periodontopathic bacteria induce Cilengitide various cytokines including TNF. It has been shown that of TNF is upregulated in peri odontitis, e. g, in gingival crevicular fluid and in gingival tissues. Therefore, periodontopathic bac teria including P. gingivalis induce the production of cytokines including TNF in periodontal tissues.

E cess TNF in periodontal tissues activates gingival epithelial cells and increases the possibility of P. gingi valis invasion in the cells, resulting in persistence of P. ginigvalis infection and prolongation thenthereby of immune re sponses in periodontal tissues. Conclusions We demonstrated that P. ginigvalis invasion into human gingival epithelial cells was enhanced by stimulation with TNF. TNF in periodontal tissues, the production of which is induced by plaque bacteria including P. gingivlis and is increased by diabetes, may lead to persistent in fection of P. ginigvalis and prolongation of immune re sponses in periodontal tissues. Methods Bacte