TY - JOUR
T1 - Porphyromonas gingivalis induce apoptosis in human gingival epithelial cells through a gingipain-dependent mechanism
AU - Stathopoulou, Panagiota G.
AU - Galicia, Johnah C.
AU - Benakanakere, Manjunatha R.
AU - Garcia, Carlos A.
AU - Potempa, Jan
AU - Kinane, Denis F.
N1 - Funding Information:
The authors thank Dr. M. Curtis and Dr. K. Nakayama for providing the gin-gipain-deficient mutants. This work was supported by US Public Health Service, National Institutes of Health, NIDCR grant DE017384 to DFK.
PY - 2009
Y1 - 2009
N2 - Background. The oral pathogen Porphyromonas gingivalis 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 P. gingivalis 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 P. gingivalis proteases arginine and lysine gingipains are necessary and sufficient to induce host cell apoptosis. Thus, live P. gingivalis 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, P. gingivalis 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 P. gingivalis elicited apoptosis.
AB - Background. The oral pathogen Porphyromonas gingivalis 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 P. gingivalis 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 P. gingivalis proteases arginine and lysine gingipains are necessary and sufficient to induce host cell apoptosis. Thus, live P. gingivalis 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, P. gingivalis 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 P. gingivalis elicited apoptosis.
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U2 - 10.1186/1471-2180-9-107
DO - 10.1186/1471-2180-9-107
M3 - Article
C2 - 19473524
AN - SCOPUS:67649352262
SN - 1471-2180
VL - 9
JO - BMC Microbiology
JF - BMC Microbiology
M1 - 107
ER -