gingivalis invasion (Figures 6 and 8). Adhesion of P. gingivalis to host cells is multimodal and involves the interaction of bacterial cell surface adhesins with receptors expressed on the surfaces of epithelial cells. Adhesion of P. gingivalis to host cells is mediated by many extracellular components, including fimbriae, proteases, hemagglutinins,

and lipopolysaccharides (LPS). Among the large array of virulence factors produced by P. gingivalis, the major fimbriae (FimA), as well as cysteine proteinases (gingipains), contribute to the attachment to and invasion of oral epithelial cells [49,50]. On the other hand, integrins can act as receptors for the integrin-binding proteins of P5091 datasheet several bacterial species [51–53]. P. gingivalis also associates with β1 and α5β1 integrin heterodimers via FimA. αVβ3 integrin also mediates fimbriae adhesion to epithelial cells [48]. In addition, carbohydrate chains on epithelial cell membrane selleck products glycolipids have been reported to act as receptors for P. gingivalis [54]. It has been demonstrated that ICAM-1 is required for the invasion of P. gingivalis into human oral epithelial cells [36]. Various cytokines including TNF-α induce expression of ICAM-1 [55,56]. Therefore,

ICAM-1 expresion and this website P. gingivalis 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 intracellular bacteria are present in IL-6-treated cells that

have an increasing amount of Rab5 [41]. These results indicate Selleck Hydroxychloroquine that overexpression 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 exacerbate the immune response. At periodontal sites, such phenomena could occur. Periodontopathic bacteria induce various cytokines including TNF-α. It has been shown that of TNF-α is upregulated in periodontitis, e.g., in gingival crevicular fluid [23] and in gingival tissues [24]. Therefore, periodontopathic bacteria including P. gingivalis induce the production of cytokines including TNF-α in periodontal tissues. Excess TNF-α in periodontal tissues activates gingival epithelial cells and increases the possibility of P. gingivalis invasion in the cells, resulting in persistence of P. ginigvalis infection and prolongation of immune responses in periodontal tissues. Conclusions We demonstrated that P. ginigvalis invasion into human gingival epithelial cells was enhanced by stimulation with TNF-α. TNF-α in periodontal tissues, the production of which is induced by plaque bacteria including P. gingivlis and is increased by diabetes, may lead to persistent infection of P. ginigvalis and prolongation of immune responses in periodontal tissues. Methods Bacterial strains and growth conditions P.