Intrinsic apoptotic pathways of gingival epithelial cells modulated by Porphyromonas gingivalis.
Porphyromonas gingivalis can inhibit chemically induced apoptosis in primary cultures of gingival epithelial cells through blocking activation of the effector caspase-3. The anti-apoptotic phenotype of P. gingivalis is conserved across strains and does not depend on the presence of fimbriae, as fimbriae-deficient mutants and a naturally occurring non-fimbriated strain were able to impede apoptosis. To dissect the survival pathways modulated by P. gingivalis, protein and gene expression of a number of components of apoptotic death pathways were investigated. P. gingivalis infection of epithelial cells resulted in the phosphorylation of JAK1 and Stat3. Quantitative real-time reverse transcription polymerase chain reaction showed that expression of Survivin and Stat3 itself, targets of activated Stat3, were elevated in P. gingivalis-infected cells. siRNA knockdown of JAK1, in combination with knockdown of Akt, abrogated the ability of P. gingivalis to block apoptosis. In contrast, cIAP-1 and cIAP-2 were not differentially regulated at either the protein or mRNA levels by P. gingivalis. One mechanism by which P. gingivalis can block apoptotic pathways in gingival epithelial cells therefore is through manipulation of the JAK/Stat pathway that controls the intrinsic mitochondrial cell death pathways. Induction of a pro-survival phenotype may prevent programmed host cell death and aid survival of P. gingivalis within gingival epithelial cells.
Mao
Song
S
Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL 32610, USA.
Park
Yoonsuk
Y
Hasegawa
Yoshiaki
Y
Tribble
Gena D
GD
James
Chlöe E
CE
Handfield
Martin
M
Stavropoulos
M Franci
MF
Yilmaz
Ozlem
O
Lamont
Richard J
RJ
D017209:Apoptosis; D016866:Bacteroidaceae Infections / Q000382:microbiology / Q000473:pathology*; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000382:microbiology / Q000502:physiology*; D005881:Gingiva / Q000382:microbiology / Q000473:pathology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D053613:Janus Kinase 1 / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism; D016966:Porphyromonas gingivalis / Q000502:physiology*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D000077022:Survivin; D044767:Ubiquitin-Protein Ligases
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000077022:Survivin; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases; D053613:Janus Kinase 1; D053148:Caspase 3