Induction of Apoptotic Cell Death by Oral Streptococci in Human Periodontal Ligament Cells

Initiation and progression of oral infectious diseases are associated with streptococcal species. Bacterial infection induces inflammatory responses together with reactive oxygen species (ROS), often causing cell death and tissue damage in the host. In the present study, we investigated the effects of oral streptococci on cytotoxicity and ROS production in human periodontal ligament (PDL) cells. showed cell cytotoxicity in a dose- and time-dependent manner. The cytotoxicity might be due to apoptosis since increased annexin V-positive cells, and the cytotoxicity was reduced by an apoptosis inhibitor, Z-VAD-FMK. Other oral streptococci such as , , and also induced apoptosis, whereas did not. All streptococci tested except triggered ROS production in human PDL cells. Interestingly, however, streptococci-induced apoptosis appears to be ROS-independent, as the cell death induced by was not recovered by the ROS inhibitor, resveratrol or -acetylcysteine. Instead, hydrogen peroxide (HO) appears to be important for the cytotoxic effects of streptococci since most oral streptococci except generated HO, and the cytotoxicity was dramatically reduced by catalase. Furthermore, streptococcal lipoproteins are involved in cytotoxicity, as we observed that cytotoxicity induced by the lipoprotein-deficient mutant was less potent than that by the wild-type and was attenuated by anti-TLR2-neutralizing antibody. Indeed, lipoproteins purified from alone were sufficient to induce cytotoxicity. Notably, lipoproteins did not induce HO or ROS but cooperatively induced cell death when co-treated with HO. Taken together, these results suggest that most oral streptococci except efficiently induce damage to human PDL cells by inducing apoptotic cell death with bacterial HO and lipoproteins, which might contribute to the progression of oral infectious diseases such as apical periodontitis.