Temporal activation of anti- and pro-apoptotic factors in human gingival fibroblasts infected with the periodontal pathogen, Porphyromonas gingivalis: potential role of bacterial proteases in host signalling

BMC Microbiology
Sonya UrnoweySailen Barik

Abstract

Porphyromonas gingivalis is the foremost oral pathogen of adult periodontitis in humans. However, the mechanisms of bacterial invasion and the resultant destruction of the gingival tissue remain largely undefined. We report host-P. gingivalis interactions in primary human gingival fibroblast (HGF) cells. Quantitative immunostaining revealed the need for a high multiplicity of infection for optimal infection. Early in infection (2-12 h), P. gingivalis activated the proinflammatory transcription factor NF-kappa B, partly via the PI3 kinase/AKT pathway. This was accompanied by the induction of cellular anti-apoptotic genes, including Bfl-1, Boo, Bcl-XL, Bcl2, Mcl-1, Bcl-w and Survivin. Late in infection (24-36 h) the anti-apoptotic genes largely shut down and the pro-apoptotic genes, including Nip3, Hrk, Bak, Bik, Bok, Bax, Bad, Bim and Moap-1, were activated. Apoptosis was characterized by nuclear DNA degradation and activation of caspases-3, -6, -7 and -9 via the intrinsic mitochondrial pathway. Use of inhibitors revealed an anti-apoptotic function of NF-kappa B and PI3 kinase in P. gingivalis-infected HGF cells. Use of a triple protease mutant P. gingivalis lacking three major gingipains (rgpA rgpB kgp) suggested a role of some...Continue Reading

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Citations

Oct 20, 2006·Journal of Virology·Vira BitkoSailen Barik
Aug 18, 2012·International Journal of Dentistry·M T PöllänenV-J Uitto
Sep 13, 2013·BMC Microbiology·Paulo C Carvalho-FilhoRoberto Meyer
Oct 31, 2012·Journal of Periodontology·Ceilidh MarchantP Mark Bartold
Jan 21, 2012·Connective Tissue Research·Eric RöhnerNicole Pischon
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Apr 27, 2007·FEMS Microbiology Letters·Georg A RothEvanthia Lalla
Jan 31, 2020·Frontiers in Neurology·Liyuan FanYuming Xu
Jan 6, 2019·Apoptosis : an International Journal on Programmed Cell Death·M R BenakanakereD F Kinane
Feb 20, 2020·Brazilian Oral Research·Manuella Verdinelli de Paula ReisCamilla Christian Gomes Moura

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Methods Mentioned

BETA
nuclear translocation
biopsies
fluorescence microscopy
PCR

Software Mentioned

Premier Biosoft
Beacon Designer

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