Porphyromonas gingivalis induce apoptosis in human gingival epithelial cells through a gingipain-dependent mechanism

Stathopoulou, Panagiota G.; Galicia, Johnah C.; Benakanakere, Manjunatha R.; García, Carlos; Potempa, Jan; Kinane, Denis F.

doi:10.1186/1471-2180-9-107

Cited by 88 publications

(91 citation statements)

References 29 publications

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“…The up-regulation of Bcl-2 was observed in epithelial cells in response to Porphyromonas gingivalis gingipains, [27,28] which indicates that this bacteria can survive in the cellular environment by evading the host immune response.…”

Section: Discussionmentioning

confidence: 99%

Porphyromonas gingivalis HmuY stimulates expression of Bcl-2 and Fas by human CD3+ T cells

et al. 2013

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BackgroundApoptosis is a highly controlled process of cell death that can be induced by periodontopathogens. The present study aimed to investigate the expression of Fas and Bcl-2 proteins by CD3+ T cells in vitro under stimulation by total Porphyromonas gingivalis antigens and purified recombinant P. gingivalis HmuY protein.ResultsCD3+ T cells derived from CP patients and stimulated with HmuY expressed higher levels of Bcl-2 compared to identical cells stimulated with P. gingivalis crude extract or cells derived from NP control subjects (p = 0.043).ConclusionThe authors hypothesize that P. gingivalis HmuY plays a role in the pathogenesis of chronic periodontitis, possibly by reducing or delaying apoptosis in T cells through a pathway involving the Bcl-2 protein.

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Section: Discussionmentioning

confidence: 99%

Porphyromonas gingivalis HmuY stimulates expression of Bcl-2 and Fas by human CD3+ T cells

et al. 2013

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“…No gross differences in tissue integrity were observed between P. gingivalisand mock-infected animals (data not shown). W83 was heat killed at 60°C for 1 h, which also inactivates the proteases (gingipains) (64). When the survival rates of Drosophila animals infected with live and heat-killed W83 were compared (Fig.…”

Section: Resultsmentioning

confidence: 99%

Porphyromonas gingivalis Virulence in a Drosophila melanogaster Model

et al. 2011

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Porphyromonas gingivalis has been implicated in the etiology of adult periodontitis. In this study, we examined the viability of Drosophila melanogaster as a new model for examining P. gingivalis-host interactions. P. gingivalis (W83) infection of Drosophila resulted in a systemic infection that killed in a dose-dependent manner. Differences in the virulence of several clinically prevalent P. gingivalis strains were observed in the Drosophila killing model, and the results correlated well with studies in mammalian infection models and human epidemiologic studies. P. gingivalis pathobiology in Drosophila did not result from uncontrolled growth of the bacterium in the Drosophila hemolymph (blood) or overt damage to Drosophila tissues. P. gingivalis killing of Drosophila was multifactorial, involving several bacterial factors that are also involved in virulence in mammals. The results from this study suggest that many aspects of P. gingivalis pathogenesis in mammals are conserved in Drosophila, and thus the Drosophila killing model should be useful for characterizing P. gingivalis-host interactions and, potentially, polymicrobe-host interactions.Porphyromonas gingivalis is a Gram-negative, obligate anaerobe that has been strongly implicated in the etiology of adult (chronic) periodontitis (21, 29), a destructive disease that affects the gums and supporting structures of the teeth. P. gingivalis-host interactions have previously been studied using several animal models, the most common of which are murine models (5,7,18,20,28), including an abscess model (39), a subcutaneous chamber model (24), and a periodontal bone loss model (41). Studies performed using murine models have demonstrated that P. gingivalis strains vary in their ability to cause periodontal bone loss (20, 40) and soft tissue destruction and death (28,43,56) and that strain W83 is highly virulent relative to many other strains of P. gingivalis (28,43,56). Murine models have also been used to identify P. gingivalis components that are important for pathogenesis (25,43,51,59) and to characterize the host response to P. gingivalis infection (6,11,31,35).The fruit fly, Drosophila melanogaster, has been well established as a nonmammalian model for studying host-pathogen interactions (1,17,52,55,63). Drosophila relies solely on an innate immune response to combat invading microbes, and this immune response strongly parallels the mammalian innate immune response (47,48). Like the mammalian innate immune response, Drosophila uses pattern recognition receptors to detect conserved microbial motifs on invading microbes, and the flies activate an immune response that is specific for the type of invading microbe. The absence of an adaptive immune response makes Drosophila useful for studying the interactions between microbes and the host innate immune response, in isolation. Numerous tools exist for the genetic manipulation of Drosophila, and these have been used to generate thousands of transgenic and mutant lines, including lines useful for identifying host fac...

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“…2A). The time points for this chronic infection were carefully chosen based on our previously published results on P. gingivalisinduced inflammatory cytokine response in gingival epithelial cells (Eskan et al 2008;Stathopoulou et al 2009;Stathopoulou et al 2010). By using this method, we successfully induced tolerance to P. gingivalis (live bacteria at MOI: 5) in normal epithelial cells.…”

Section: Chronic P Gingivalis Infection Modelmentioning

confidence: 99%

TLR2 Promoter Hypermethylation Creates Innate Immune Dysbiosis

et al. 2014

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Periodontitis is a common chronic inflammatory disease that is initiated by a complex microbial biofilm that poses significant health and financial burdens globally. Porphyromonas gingivalis is a predominant pathogen that maintains chronic inflammatory periodontitis. Toll-like receptors (TLRs) play an important role in periodontitis by recognizing pathogens and maintaining tissue homeostasis. Deficiencies in TLR expression and downstream signaling may reduce the host's innate defenses against pathogens, leading to bacterial persistence and exacerbated inflammation, which are now being better appreciated in disease pathologies. In the case of periodontitis, gingival epithelial cells form the first line of defense against pathogens. Innate immune dysregulation in these cells relates to severe disease pathology. We recently identified a blunted TLR2 expression in certain gingival epithelial cells expressing diminished cytokine signaling upon P. gingivalis stimulation. Upon detailed analysis of the TLR2 promoter CpG Island, we noted higher CpG methylation in this dysregulated cell type. When these cells were treated with DNA methyltransferase inhibitor, TLR2 mRNA and cytokine expression were significantly increased. If TLR2 expression plasmid was ectopically expressed in dysfunctional cells prior to P. gingivalis stimulation, the cytokine expression was increased, confirming the requirement of TLR2 in the P. gingivalis-mediated inflammatory response. We designed a chronic in vitro infection model to test if P. gingivalis can induce DNA methylation in normal gingival epithelial cells that express higher TLR2 upon agonist stimulation. Chronic treatment of normal epithelial cells with P. gingivalis introduced de novo DNA methylation within the cells. In addition, increased DNA methylation was observed in the gingiva of mice infected with P. gingivalis in a periodontitis oral gavage model. Moreover, tissues obtained from periodontitis patients also exhibited differential TLR2 promoter methylation, as revealed by bisulfite DNA sequencing. Taken together, DNA methylation of TLR2 can modulate host innate defense mechanisms that may confer increased disease susceptibility.

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Porphyromonas gingivalis induce apoptosis in human gingival epithelial cells through a gingipain-dependent mechanism

Cited by 88 publications

References 29 publications

Porphyromonas gingivalis HmuY stimulates expression of Bcl-2 and Fas by human CD3+ T cells

Porphyromonas gingivalis HmuY stimulates expression of Bcl-2 and Fas by human CD3+ T cells

Porphyromonas gingivalis Virulence in a Drosophila melanogaster Model

TLR2 Promoter Hypermethylation Creates Innate Immune Dysbiosis

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