Porphyromonas gingivalis antigens differently participate in the proliferation and cell death of human PBMC

Trindade, Soraya Castro; Olczak, Teresa; Filho, Isaac Suzart Gomes; Moura-Costa, Lília Ferreira de; Vale, Vera Lúcia Costa; Galdino-Neto, Milton; Alves, Heloísa Helena de Oliveira; Carvalho-Filho, Paulo Cirino de; Sampaio, Geraldo Pedral; Xavier, Márcia Tosta; Sarmento, Viviane Almeida; Meyer, Roberto

doi:10.1016/j.archoralbio.2011.09.003

Cited by 19 publications

(14 citation statements)

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“…Recent data [25] has shown that P. gingivalis total antigens, as well as purified recombinant P. gingivalis HmuY, stimulate late apoptosis in PBMCs derived from CP patients. This finding suggests that although the protein is capable of signaling the apoptotic pathway, the stimulated cell is unable to terminate the apoptotic process that leads to cell death, thereby secondary necrosis is the resulting mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…Other investigations have been done to confirm or refute these preliminary findings. It’s important to emphasize that the concentrations employed for each antigen was previously tested [6,25,29]. In this study, it was used 2.5 μg/mL of HmuY versus 0.5 μg/mL of crude extract (5fold more of the recombinant protein).…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, the inhibition of Bcl-2 in individuals without periodontitis may be one of the underlying mechanisms that prevent these individuals from developing the disease. A recent report that evaluated individuals with similar clinical characteristics [25] revealed that HmuY induced delayed apoptosis, as evidenced by the fact that cultivated cells stimulated with this recombinant protein presented concomitant labeling with annexin V and propidium iodide.…”

Section: Discussionmentioning

confidence: 99%

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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%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2013

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“…(27) Tem sido observado que HmuY consiste num fator de virulência importante, levando à inibição da proliferação celular; indução de apoptose tardia, por estimular a expressão de Bcl-2; (16) e indução de necrose em Células Mononucleares de Sangue Periférico de indivíduos com periodontite crônica. (28)…”

Section: Doença Periodontal: Dos Primórdios à Classificação Atualunclassified

Porphyromonas Gingivalis E Periodontite Crônica - Avanços Recentes

et al. 2016

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A periodontite é multifatorial e acomete tecidos circundantes dos dentes. Sua etiologia inclui microrganismos como Porphyromonas gingivalis, Tannerella forsythia e Aggregatibacter actinomycetemcomitans. Este trabalho objetivou discutir o papel de Porphyromonas gingivalis na periodontite crônica. Foram pesquisadas as bases eletrônicas PubMed, BIREME e SciELO, buscando aspectos históricos e estudos publicados entre 2000 e 2015, usando, em português e inglês, os descritores: “Periodontite Crônica”, “Porphyromonas gingivalis” e “Fatores de virulência”. Foram encontrados 205 artigos e 24 foram incluídos. Foram selecionados registros sobre doenças periodontais dos primórdios civilizatórios até os dias atuais. Sua prevalência na população mundial permanece alta e diversas pesquisas abordam a etiopatogenia da doença. P. gingivalis é capaz de induzir resposta humoral e celular nos indivíduos infectados. Estudos sobre seus mecanismos de escape e fatores de virulência relatam dano tecidual consequente à resposta imuno-inflamatória exacerbada do hospedeiro que pode evoluir para edentulismo. Estudos da resposta imune a P. gingivalis sugerem seu papel na perpetuação do estado inflamatório por interferir na produção de citocinas e em mecanismos de morte celular em tecidos do hospedeiro, resultando em destruição tecidual. Os conhecimentos atuais sobre mecanismos de infecção e fatores de virulência de P. gingivalis indicam seu papel como componente-chave na periodontite crônica.

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“…Other molecules derived from P. gingivalis also have the capacity to modulate the immune response in peripheral blood mononuclear cells (PBMC) . Among them is HmuY protein, which is capable of inducing increased levels of IL‐1β and IL‐10 and inhibiting production of IL‐8 .…”

Section: Introductionmentioning

confidence: 99%

Production of interferon‐gamma, interleukin‐6, and interleukin‐1β by human peripheral blood mononuclear cells stimulated with novel lys‐gingipain synthetic peptides

Santos-Lima

Oliveira

Santos

et al. 2019

Journal of Periodontology

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Background: Periodontitis is a progressive inflammatory process, and its pathogenesis is related to the presence of a dysbiotic subgingival biofilm that elicits the immune response. Porphyromonas gingivalis is a keystone pathogen, and its Lys-gingipain (Kgp) virulence factor is involved in the pathogen-host interaction through the production of cytokines by host cells, but the specific mechanisms of this interaction have not been elucidated. The present study evaluated the in vitro production of interferongamma (IFN-), interleukin (IL)-6, and IL-1 cytokines in response to antigenic stimulation of peripheral blood mononuclear cells (PBMCs) with novel Kgp synthetic peptides. Methods:Our previous in silico study predicted 16 immunogenic peptides from Kgp protein. Nine peptides derived from different regions of the protein were chemically synthesized. The synthetic peptides Kgp12, 17, and 18 were selected based on the immunoglobulin G immunoreactivity in the serum of patients with periodontitis (P) and individuals without periodontitis (WP), and they were used in in vitro stimulation of PBMC derived from groups P and WP. Enzyme-linked immunosorbent assay and microsphere-based flow cytometric assay were used to verify the levels of the cytokines produced in PBMC cultures after 48 hours.Results: Kgp12, 17, and 18 peptides induced lower production of IFN-. Kgp12 induced higher levels of IFN-in WP than in P individuals. Kgp12 induced higher production of IL-6 and IL-1 compared with the other stimuli. Conclusion:The novel Kgp synthetic peptides tested herein are immunogenic peptides (epitopes) since they induced the production of cytokines by PBMC and therefore may be useful tools in evaluating the pathogen-host interaction. K E Y W O R D Scytokines, immunology, microbiology, periodontitis J Periodontol. 2019;90:993-1001.

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Porphyromonas gingivalis antigens differently participate in the proliferation and cell death of human PBMC

Abstract: The inhibitory effect of cell proliferation caused by Pg LPS and HmuY protein is not observed when these antigens comprise Pg extract. Despite induced apoptosis, some still unknown mechanism determines the inflammatory outcome in cell death stimulated by HmuY.

Cited by 19 publications

References 44 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 E Periodontite Crônica - Avanços Recentes

Production of interferon‐gamma, interleukin‐6, and interleukin‐1β by human peripheral blood mononuclear cells stimulated with novel lys‐gingipain synthetic peptides

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