Intrinsic apoptotic pathways of gingival epithelial cells modulated by Porphyromonas gingivalis

Song Mao, Yoonsuk Park, Yoshiaki Hasegawa, Gena D. Tribble, Chlöe E. James, Martin Handfield, M. Franci Stavropoulos, Özlem Yilmaz, Richard J. Lamont

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1997-2007
Number of pages11
JournalCellular Microbiology
Volume9
Issue number8
DOIs
StatePublished - Aug 2007

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

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