<it>Porphyromonas gingivalis </it>induce apoptosis in human gingival epithelial cells through a gingipain-dependent mechanism

Garcia Carlos A; Benakanakere Manjunatha R; Galicia Johnah C; Stathopoulou Panagiota G; Potempa Jan; Kinane Denis F

<it>Porphyromonas gingivalis </it>induce apoptosis in human gingival epithelial cells through a gingipain-dependent mechanism

2009

Abstract Background The oral pathogen <it>Porphyromonas gingivalis </it>has been shown to modulate apoptosis in different cell types, but its effect on epithelial cells remains unclear. Results We demonstrate that primary human gingival epithelial cells (HGECs) challenged with live <it>P. gingivalis </it>for 24 hours exhibit apoptosis, and we characterize this by M30 epitope detection, caspase-3 activity, DNA fragmentation and Annexin-V staining. Live bacteria strongly upregulated intrinsic and extrinsic apoptotic pathways. Pro-apoptotic molecules such as caspase-3, -8, -9, Bid and Bax were upregulated after 24 hours. The anti-apoptotic Bcl-2 was also upregulated, but this was not sufficient to ensure cell survival. The main <it>P. gingivalis </it>proteases arginine and lysine gingipains are necessary and sufficient to induce host cell apoptosis. Thus, live <it>P. gingivalis </it>can invoke gingival epithelial cell apoptosis in a time and dose dependent manner with significant apoptosis occurring between 12 and 24 hours of challenge via a gingipain-dependent mechanism. Conclusion The present study provides evidence that live, but not heat-killed, <it>P. gingivalis </it>can induce apoptosis after 24 hours of challenge in primary human gingival epithelial cells. Either arginine or lysine gingipains are necessary and sufficient factors in <it>P. gingivalis </it>elicited apoptosis.

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