<it>Porphyromonas gingivalis </it>induce apoptosis in human gingival epithelial cells through a gingipain-dependent mechanism
2009
Garcia Carlos A | Benakanakere Manjunatha R | Galicia Johnah C | Stathopoulou Panagiota G | Potempa Jan | Kinane Denis F
<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p>
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