gingivalis, indicating that this chemokine is regulated by some additional mechanism beside that of heat-instable gingipains. For instance, a study by Ohno et al. showed that CXCL10 and CCL5 gene is induced by P. gingivalis in osteoblasts and ST2 mouse stromal cells and that NFκB inhibitor suppressed CCL5 expression but not CXCL10 [29]. This suggest that P. gingivalis modulates CXCL10 gene expression through an NFκB-independent pathway. Of further interest, the expression of CXCL10 is increased in autoimmunity diseases like rheumatoid arthritis and multiple sclerosis. For instance, Lee see more et al. reported that CXCL10 contributes to bone-resorption by inducing osteoclast formation

in rheumatoid arthritis via induction of receptor activator of NFκB ligand (RANKL) [27]. However, since bone-resorption is a hallmark of progressive periodontitis,

our results may indicate that CXCL10 plays a minor role when it comes to bone-resorption since even heat-killed P. gingivalis totally suppressed CXCL10. Besides, high levels of CXCL10 have receptor-independent anti-microbial properties. Even though it is questionable if such high levels (about 1 μM), i.e. concentrations 100-fold higher than needed for chemotactic function, are realistic in vivo, Prost and colleagues showed that this antimicrobial activity is achievable in vitro and may be an important response against bacterial infection [30]. check details Thus, the strong suppressive effect of CXCL10 by both viable and heat-killed P. gingivalis may in this case be beneficial for a sustained P. gingivalis infection. Anyway, further research is needed about the regulation of CXCL10 and its signaling pathways as well as its cAMP role in bacterial infection. Serpin-1 (also known as plasminogen activator inhibitor 1), was continuously expressed regardless of stimulation with

TNF-α and/or bacteria. Serpin-1 plays an integrated part of the plasmin system, working as an inhibitor of tissue plasminogen activator as well as urokinase plasminogen activator, both of which converts plasminogen to plasmin. Interestingly, serpin-1 has been implicated in fibroblast senescent. Serpin-1 is induced by various growth factors and has been suggested to be a down-stream target of p53, where p53 controls growth factor-dependent proliferation by upregulating serpin-1 [31]. However, the fibroblast strains in our experiments were used at low passages. Conclusion In conclusion, our results show that a broad range of fibroblast-derived inflammatory mediators are inactivated by P. gingivalis due to proteolytic activities of gingipains, whereby the bacteria can create a more favourable milieu where it can evade the host immune GSK1904529A purchase system and promote its own growth and establishment. Also, by differentially regulate the inflammatory mediators, such as CXCL10 and TNF-α, P.