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1.
PLoS One ; 15(9): e0238425, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32960889

RESUMO

OBJECTIVE: To evaluate the effects of Bifidobacterium animalis subsp. lactis HN019 (HN019) on clinical periodontal parameters (plaque accumulation and gingival bleeding), on immunocompetence of gingival tissues [expression of beta-defensin (BD)-3, toll-like receptor 4 (TLR4), cluster of differentiation(CD)-57 and CD-4], and on immunological properties of saliva (IgA levels) in non-surgical periodontal therapy in generalized chronic periodontitis (GCP) patients. Adhesion to buccal epithelial cells (BEC) and the antimicrobial properties of HN019 were also investigated. MATERIALS AND METHODS: Thirty patients were recruited and monitored clinically at baseline (before scaling and root planing-SRP) and after 30 and 90 days. Patients were randomly assigned to Test (SRP+Probiotic, n = 15) or Control (SRP+Placebo, n = 15) group. Probiotic lozenges were used for 30 days. Gingival tissues and saliva were immunologically analyzed. The adhesion of HN019 with or without Porphyromonas gingivalis in BEC and its antimicrobial properties were investigated in in vitro assays. Data were statistically analyzed (p<0.05). RESULTS: Test group presented lower plaque index (30 days) and lower marginal gingival bleeding (90 days) when compared with Control group. Higher BD-3, TLR4 and CD-4 expressions were observed in gingival tissues in Test group than in Control group. HN019 reduced the adhesion of P. gingivalis to BEC and showed antimicrobial potential against periodontopathogens. CONCLUSION: Immunological and antimicrobial properties of B. lactis HN019 make it a potential probiotic to be used in non-surgical periodontal therapy of patients with GCP. CLINICAL RELEVANCE: B. lactis HN019 may be a potential probiotic to improve the effects of non-surgical periodontal therapy. Name of the registry and registration number (ClinicalTrials.gov): "Effects of probiotic therapy in the treatment of periodontitis"-NCT03408548.


Assuntos
Bifidobacterium animalis/imunologia , Periodontite Crônica/terapia , Probióticos/uso terapêutico , Adulto , Aderência Bacteriana/imunologia , Infecções por Bacteroidaceae/imunologia , Infecções por Bacteroidaceae/microbiologia , Infecções por Bacteroidaceae/terapia , Periodontite Crônica/imunologia , Periodontite Crônica/microbiologia , Método Duplo-Cego , Feminino , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Imunoglobulina A Secretora/metabolismo , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/imunologia , Mucosa Bucal/microbiologia , Porphyromonas gingivalis/patogenicidade , Saliva/imunologia
2.
Arch Oral Biol ; 114: 104695, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32315811

RESUMO

OBJECTIVE: To analyse the citrulline level in the periodontium in association with the presence of or antibody levels against Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis. DESIGN: Gingival crevicular fluid (GCF), subgingival biofilm and blood serum were sampled from 98 subjects (26 with RA, 72 without RA (NoRA)). GCF was analyzed for the level of citrulline, for interleukin (IL)-1ß, IL-17, IL-10 and monocyte-chemoattractant protein (MCP)-1. Microorganisms were identified in subgingival biofilms. Antibodies againstP. gingivalis, and Aggregatibacter actinomycetemcomitans were quantified in serum. RESULTS: GCF citrulline level was the lowest (by trend) in NoRA group without periodontitis. In NoRA, but not in RA an association between GCF citrulline level and P. gingivalis antibody levels was found and the GCF citrulline levels were higher in P. gingivalis positive samples. Any association of A. actinomycetemcomitans with GCF citrulline level did not exist. A model of univariate variance analysis (p = 0.001) showed a dependence of GCF citrulline level from the number of sites with PD (probing depth) ≥5 mm (p = 0.003) and the GCF MCP-1/CCL2 level (p = 0.019). Compared with NoRA in RA the number of teeth was lower, the number of sites with PD ≥ 5 mm was less, GCF levels of interleukin-17 and MCP-1/CCL2 were higher and those of IL-10 lower. Yeasts were only cultured in 15 RA patients (p < 0.001). CONCLUSION: Citrullination in periodontium might be associated with P. gingivalis supporting the potential role as a trigger in the development of RA. Pathogenesis of periodontal disease in RA patients seems to differ from that in NoRA and should be investigated further.


Assuntos
Artrite Reumatoide/complicações , Citrulinação , Citrulina/análise , Periodontite/microbiologia , Periodonto/química , Aggregatibacter actinomycetemcomitans , Infecções por Bacteroidaceae/patologia , Líquido do Sulco Gengival , Humanos , Periodonto/microbiologia , Porphyromonas gingivalis/patogenicidade
3.
Sci Rep ; 10(1): 4134, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-32139740

RESUMO

Odontogenic infection of Porphyromonas gingivalis (P.g.), a major periodontal pathogen, exacerbates pathological progression of non-alcoholic steatohepatitis (NASH). In this study, we aimed to clarify the detailed mechanism in which P.g. induced hepatic stellate cells (HSCs; key effector cells in liver fibrosis) activation. In the liver of high fat diet-induced NASH mouse model with P.g. odontogenic infection, immunolocalization of P.g. was detected. The number of hepatic crown-like structure, which was macrophage aggregation and related to liver fibrosis, was drastically increased and fibrosis area was also increased through upregulating immunoexpression of Phosphorylated Smad2 (key signaling molecule of TGF-ß1) and Galectin-3. P.g.-secreted trypsin-like enzyme [gingipain; an activator of protease-activated receptor 2 (PAR2)] stimulated HSC proliferation and differentiation through Smad and ERK signaling induced by TGF-ß1 produced from HSCs with P.g.-infection. Further, Galectin-3 produced from HSCs with P.g. infection and P.g.-derived LPS/lipoprotein stimulation stabilized TGFß-receptor II resulting in increasing sensitivity for TGF-ß1, finally leading to HSC differentiation via activating Smad and ERK signaling. In addition to them, hepatocytes (main component cells of liver) contributed to HSC activation through TGF-ß1 and Galectin-3 production in paracrine manner. Collectively, P.g.-odontogenic infection exacerbates fibrosis of NASH by HSC activation through TGF-ß1 and Gal-3 production from HSCs and hepatocytes.


Assuntos
Cirrose Hepática/microbiologia , Cirrose Hepática/patologia , Hepatopatia Gordurosa não Alcoólica/microbiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Porphyromonas gingivalis/patogenicidade , Animais , Western Blotting , Diferenciação Celular/fisiologia , Linhagem Celular , Proliferação de Células/fisiologia , Ensaio de Imunoadsorção Enzimática , Granuloma/metabolismo , Granuloma/microbiologia , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/microbiologia , Hepatócitos/metabolismo , Imuno-Histoquímica , Cirrose Hepática/metabolismo , Camundongos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
4.
Cell Mol Life Sci ; 77(14): 2751-2769, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32002588

RESUMO

Atherosclerotic vascular disease (ASVD) is a chronic process, with a progressive course over many years, but it can cause acute clinical events, including acute coronary syndromes (ACS), myocardial infarction (MI) and stroke. In addition to a series of typical risk factors for atherosclerosis, like hyperlipidemia, hypertension, smoking and obesity, emerging evidence suggests that atherosclerosis is a chronic inflammatory disease, suggesting that chronic infection plays an important role in the development of atherosclerosis. Toll-like receptors (TLRs) are the most characteristic members of pattern recognition receptors (PRRs), which play an important role in innate immune mechanism. TLRs play different roles in different stages of infection of atherosclerosis-related pathogens such as Chlamydia pneumoniae (C. pneumoniae), periodontal pathogens including Porphyromonas gingivalis (P. gingivalis), Helicobacter pylori (H. pylori) and human immunodeficiency virus (HIV). Overall, activation of TLR2 and 4 seems to have a profound impact on infection-related atherosclerosis. This article reviews the role of TLRs in the process of atherosclerosis after C. pneumoniae and other infections and the current status of treatment, with a view to providing a new direction and potential therapeutic targets for the study of ASVD.


Assuntos
Aterosclerose/genética , Infecções Bacterianas/genética , Infecções por HIV/genética , Receptores Toll-Like/genética , Aterosclerose/complicações , Aterosclerose/microbiologia , Aterosclerose/virologia , Infecções Bacterianas/complicações , Infecções Bacterianas/microbiologia , Infecções Bacterianas/virologia , Chlamydophila pneumoniae/patogenicidade , HIV/patogenicidade , Infecções por HIV/complicações , Infecções por HIV/microbiologia , Infecções por HIV/virologia , Helicobacter pylori/patogenicidade , Humanos , Porphyromonas gingivalis/patogenicidade
5.
Biochim Biophys Acta Mol Basis Dis ; 1866(6): 165731, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32088316

RESUMO

Outer membrane vesicles (OMVs) are nanosized particles derived from the outer membrane of gram-negative bacteria. Oral bacterium Porphyromonas gingivalis (Pg) is known to be a major pathogen of periodontitis that contributes to the progression of periodontal disease by releasing OMVs. The effect of Pg OMVs on systemic diseases is still unknown. To verify whether Pg OMVs affect the progress of diabetes mellitus, we analyzed the cargo proteins of vesicles and evaluated their effect on hepatic glucose metabolism. Here, we show that Pg OMVs were equipped with Pg-derived proteases gingipains and translocated to the liver in mice. In these mice, the hepatic glycogen synthesis in response to insulin was decreased, and thus high blood glucose levels were maintained. Pg OMVs also attenuated the insulin-induced Akt/glycogen synthase kinase-3 ß (GSK-3ß) signaling in a gingipain-dependent fashion in hepatic HepG2 cells. These results suggest that the delivery of gingipains mediated by Pg OMV elicits changes in glucose metabolisms in the liver and contributes to the progression of diabetes mellitus.


Assuntos
Membrana Externa Bacteriana/metabolismo , Cisteína Endopeptidases Gingipaínas/genética , Periodontite/genética , Porphyromonas gingivalis/genética , Animais , Membrana Externa Bacteriana/patologia , Modelos Animais de Doenças , Cisteína Endopeptidases Gingipaínas/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Humanos , Resistência à Insulina/genética , Fígado/metabolismo , Fígado/microbiologia , Camundongos , Periodontite/microbiologia , Periodontite/patologia , Porphyromonas gingivalis/metabolismo , Porphyromonas gingivalis/patogenicidade , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/genética
6.
Circ Res ; 126(6): e15-e29, 2020 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-32078488

RESUMO

RATIONALE: Atherosclerotic cardiovascular diseases are the leading cause of mortality worldwide. Atherosclerotic cardiovascular diseases are considered as chronic inflammation processes. In addition to risk factors associated with the cardiovascular system itself, pathogenic bacteria such as the periodontitis-associated Porphyromonas gingivalis (P gingivalis) are also closely correlated with the development of atherosclerosis, but the underlying mechanisms are still elusive. OBJECTIVE: To elucidate the mechanisms of P gingivalis-accelerated atherosclerosis and explore novel therapeutic strategies of atherosclerotic cardiovascular diseases. METHODS AND RESULTS: Bmal1-/- (brain and muscle Arnt-like protein 1) mice, ApoE-/- mice, Bmal1-/-ApoE-/- mice, conditional endothelial cell Bmal1 knockout mice (Bmal1fl/fl; Tek-Cre mice), and the corresponding jet-legged mouse model were used. P gingivalis accelerates atherosclerosis progression by triggering arterial oxidative stress and inflammatory responses in ApoE-/- mice, accompanied by the perturbed circadian clock. Circadian clock disruption boosts P gingivalis-induced atherosclerosis progression. The mechanistic dissection shows that P gingivalis infection activates the TLRs-NF-κB signaling axis, which subsequently recruits DNMT-1 to methylate the BMAL1 promoter and thus suppresses BMAL1 transcription. The downregulation of BMAL1 releases CLOCK, which phosphorylates p65 and further enhances NF-κB signaling, elevating oxidative stress and inflammatory response in human aortic endothelial cells. Besides, the mouse model exhibits that joint administration of metronidazole and melatonin serves as an effective strategy for treating atherosclerotic cardiovascular diseases. CONCLUSIONS: P gingivalis accelerates atherosclerosis via the NF-κB-BMAL1-NF-κB signaling loop. Melatonin and metronidazole are promising auxiliary medications toward atherosclerotic cardiovascular diseases.


Assuntos
Fatores de Transcrição ARNTL/metabolismo , Aterosclerose/metabolismo , Infecções por Bacteroidaceae/complicações , Estresse Oxidativo , Fatores de Transcrição ARNTL/genética , Animais , Antibacterianos/uso terapêutico , Antioxidantes/uso terapêutico , Apolipoproteínas E/genética , Aterosclerose/tratamento farmacológico , Aterosclerose/etiologia , Aterosclerose/microbiologia , Proteínas CLOCK/metabolismo , Ritmo Circadiano , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Regulação para Baixo , Endotélio Vascular/metabolismo , Feminino , Masculino , Melatonina/uso terapêutico , Metronidazol/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Porphyromonas gingivalis/patogenicidade , Transdução de Sinais , Receptores Toll-Like/metabolismo
7.
Nutrients ; 12(1)2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31968635

RESUMO

Periodontitis is a polymicrobial infectious disease that leads to inflammation of the gingiva, resulting in teeth loss by various causes such as inflammation-mediated bone resorption. Recently, many investigators have reported that the periodontitis resulting from persistent low-grade infection of Gram-negative bacteria such as Porphyromonas gingivalis (Pg) is associated with increased atherosclerosis, diabetes mellitus, and other systemic diseases through blood stream. On the other hand, carotenoids belong among phytochemicals that are responsible for different colors of the foods. It is important to examine whether carotenoids are effective to the inhibition of periodontal infection/inflammation cascades. This review summarizes the advanced state of knowledge about suppression of periodontal infection by several carotenoids. A series of findings suggest that carotenoids intake may provide novel strategy for periodontitis treatment, although further study will be needed.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Infecções por Bacteroidaceae/tratamento farmacológico , Carotenoides/uso terapêutico , Periodontite/tratamento farmacológico , Porphyromonas gingivalis/patogenicidade , Animais , Anti-Inflamatórios/efeitos adversos , Antioxidantes/efeitos adversos , Infecções por Bacteroidaceae/microbiologia , Carotenoides/efeitos adversos , Humanos , Mediadores da Inflamação/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Periodontite/microbiologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Resultado do Tratamento
8.
Biochem J ; 477(2): 381-405, 2020 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-31899475

RESUMO

As part of the infective process, Porphyromonas gingivalis must acquire heme which is indispensable for life and enables the microorganism to survive and multiply at the infection site. This oral pathogenic bacterium uses a newly discovered novel hmu heme uptake system with a leading role played by the HmuY hemophore-like protein, responsible for acquiring heme and increasing virulence of this periodontopathogen. We demonstrated that Prevotella intermedia produces two HmuY homologs, termed PinO and PinA. Both proteins were produced at higher mRNA and protein levels when the bacterium grew under low-iron/heme conditions. PinO and PinA bound heme, but preferentially under reducing conditions, and in a manner different from that of the P. gingivalis HmuY. The analysis of the three-dimensional structures confirmed differences between apo-PinO and apo-HmuY, mainly in the fold forming the heme-binding pocket. Instead of two histidine residues coordinating heme iron in P. gingivalis HmuY, PinO and PinA could use one methionine residue to fulfill this function, with potential support of additional methionine residue/s. The P. intermedia proteins sequestered heme only from the host albumin-heme complex under reducing conditions. Our findings suggest that HmuY-like family might comprise proteins subjected during evolution to significant diversification, resulting in different heme coordination modes. The newer data presented in this manuscript on HmuY homologs produced by P. intermedia sheds more light on the novel mechanism of heme uptake, could be helpful in discovering their biological function, and in developing novel therapeutic approaches.


Assuntos
Heme/genética , Hemeproteínas/genética , Periodontite/genética , Prevotella intermedia/genética , Regulação Bacteriana da Expressão Gênica/genética , Heme/química , Hemeproteínas/química , Humanos , Ferro/metabolismo , Periodontite/microbiologia , Periodontite/patologia , Porphyromonas gingivalis/genética , Porphyromonas gingivalis/patogenicidade , Prevotella intermedia/patogenicidade , RNA Mensageiro/genética , Homologia de Sequência de Aminoácidos
9.
J Periodontal Res ; 55(1): 13-22, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31529626

RESUMO

OBJECTIVE: The target of the current systematic review is to gather and synthesize the most recent scientific information about the role of Porphyromonas gingivalis in the molecular pathways of oral squamous cell carcinoma (OSCC). BACKGROUND: Oral squamous cell carcinoma is the most common malignancy of the oral cavity, with a poor prognosis and a low survival rate. Etiology is multifactorial but consumption of tobacco and alcohol is the most important risk factors. P gingivalis is a Gram-negative anaerobic bacterium commonly found in oral microbiota that has been linked to periodontal disease (PD), and recently to OSCC. However, its association with OSCC development is not well defined. MATERIAL AND METHODS: A bibliographic research was carried out selecting articles published until 2019, on PubMed, Web of Science, and Scopus databases, with the keywords "Porphyromonas gingivalis," "oral cancer," "oral squamous cell carcinoma," and "periodontal pathogen." RESULTS: Seventeen articles, 14 in vitro and three in animal models, were selected. Models mimicking OSCC were OSCC pre-established cell lines (11 studies), OSCC/ healthy human biopsies (three studies), and animals with OSCC (three studies). P gingivalis strains used to cause infection in these studies were ATCC 33277, 381, and W83. CONCLUSIONS: Porphyromonas gingivalis could play an important role in OSCC development and could be involved in three different stages: epithelial-mesenchymal transition of malignant cells, neoplastic proliferation, and tumor invasion. Current findings emphasize the convenience of treatment and control approaches of PD as part of the primary prevention of OSCC.


Assuntos
Carcinoma de Células Escamosas/microbiologia , Neoplasias Bucais/microbiologia , Porphyromonas gingivalis/patogenicidade , Animais , Humanos
10.
Arch Oral Biol ; 109: 104529, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31574324

RESUMO

OBJECTIVE: Periodontitis disease is a chronic inflammation, and the prevention or treatment of periodontal disease is important for improving oral health and averting systemic diseases.Acer tegmentosum Maxim (ATM) is a type of deciduous tree in Korea. ATM extracts have been traditionally used to treat various dieases. This study investigated the effects of ATM extract on mitigation of periodontitis in vitro and in vivo. DESIGN: The current study investigated whether extracts ofAcer tegmentosum Maxim (ATM) attenuated periodontitis induced by Porphyromonas gingivalis-derived lipopolysaccharide (LPS) in vitro and in vivo. We used a rat model of experimental periodontitis that received oral administration of 1 mg/kg P. gingivalis-derived LPS for 10 days. Periodontitis models was treated with two different dosages of ATM (30 or 100 mg/kg) during the same period of periodontal induction for histological analysis. RESULTS: The results indicated that aqueous ATM extracts effectively ameliorated ligature-induced periodontitis through of the antibacterial, anti-oxidative, and anti-inflammatory activities. CONCLUSION: These pre-clinical results suggest the need for further studies on the anti-periodontitis effect of ATM in humans. Thus, ATM could be used as a natural anti-periodontitis agent for the treatment of periodontitis.


Assuntos
Acer/química , Periodontite/tratamento farmacológico , Extratos Vegetais/farmacologia , Porphyromonas gingivalis/patogenicidade , Animais , Linhagem Celular , Humanos , Lipopolissacarídeos , Masculino , Malondialdeído/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Periodontite/microbiologia , Casca de Planta/química , Ratos , Ratos Sprague-Dawley , República da Coreia
11.
J Periodontal Res ; 55(2): 215-220, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31691977

RESUMO

BACKGROUND AND OBJECTIVE: In the last decade, numerous studies have been published to clarify the role of probiotics, especially Lactobacillus reuteri, as an adjunct to conventional periodontal treatment. Although the health benefits of probiotics are numerous, they are live bacteria, and the administration of live organisms is not risk-free. We evaluated the antimicrobial effect of L reuteri and its cell-free culture supernatant on Porphyromonas gingivalis, a keystone periodontal pathogen, in vitro. We also evaluated the influence of this probiotic in its live, heat-killed (HKL, paraprobiotic) form and its supernatant on the Galleria mellonella invertebrate model after infection by P gingivalis. METHODS: The interaction assay was conducted with P gingivalis and L reuteri preparations (live cells and supernatant preparation). For this, P gingivalis and L reuteri preparations were added to tubes containing Brain Heart Infusion broth and incubated for 3 days. The suspensions were then seeded onto appropriate culture media for the calculation of colony-forming units per mL (CFU/mL). An in vivo assay with the G mellonella model was also performed. Live L reuteri, HKL, or supernatant was inoculated 2 hours prior to infection with P gingivalis. Survival was evaluated over 7 days, and the number of hemocytes in the hemolymph was estimated 3 hours after P gingivalis infection. Data were then subjected to statistical testing (α = 5%). RESULTS: Both live L reuteri and its supernatant had antimicrobial activity against P gingivalis (CFU reduction up to 86%, P < .05). Moreover, treatment with live and HKL had similar effects on G mellonella survival (increased survival up to 46%, P < .05). However, only live L reuteri was able to significantly increase the hemocyte density in this invertebrate model. CONCLUSION: Lactobacillus reuteri antimicrobial activity against P gingivalis and its effects on G mellonella survival after infection with a periodontopathogen do not depend on cell viability. This allows the development of products without live bacterium while maintaining similar effects.


Assuntos
Meios de Cultivo Condicionados/farmacologia , Lactobacillus reuteri , Porphyromonas gingivalis/efeitos dos fármacos , Probióticos , Animais , Temperatura Alta , Mariposas , Porphyromonas gingivalis/patogenicidade
12.
Arch Oral Biol ; 110: 104632, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31837589

RESUMO

OBJECTIVE: Porphyromonas gingivalis (P. gingivalis)-derived LPS is a major mediator of inflammation and can promote the resorption of alveolar bone in chronic periodontitis. Although the effect of P. gingivalis LPS on human periodontal ligament fibroblasts (hPDLFs) was already investigated by numerous studies, the change of whole transcriptional profile remains undefined. The aim of this study was to investigate P. gingivalis LPS induced whole transcriptional profile in hPDLFs and the expression of the genes associated with the periodontitis. MATERIALS AND METHODS: RNA-seq was performed on hPDLFs treated with or without P. gingivalis LPS. Moreover, the expression of selected inflammatory cytokines, chemokines and matrix metalloproteinases (MMPs), which contribute to periodontitis, were evaluated by quantitative RT-PCR and further measured by ELISA. RESULTS: We found that an average of 12,752 genes were detected among the different groups, and 1374 differentially expressed genes (DEGs) were identified between groups with or without P. gingivalis LPS stimulation for 24 h. However, only 36 DEGs were examined in hPDLFs exposed to P. gingivalis LPS for 24 h or 72 h. Furthermore, the mRNA levels and concentrations of interleukin 8 (IL-8), IL-6, monocyte chemotactic protein 1 (MCP-1), chemokine (CXC motif) ligand 5 (CXCL5), MMP1 and MMP3 were significantly higher in hPDLFs exposed to P. gingivalis LPS for 24 h compared to the untreated hPDLFs. CONCLUSIONS: The entire transcriptional profile of P. gingivalis LPS stimulation of hPDLFs was presented for the first time, which could provide an important basis and experimental direction for further research into the mechanisms of periodontitis.


Assuntos
Perfilação da Expressão Gênica , Ligamento Periodontal , Porphyromonas gingivalis , Células Cultivadas , Fibroblastos , Humanos , Inflamação , Lipopolissacarídeos , Ligamento Periodontal/metabolismo , Periodontite , Porphyromonas gingivalis/patogenicidade
13.
Sci Rep ; 9(1): 19379, 2019 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852912

RESUMO

The role of Porphyromonas gingivalis (P. gingivalis) or its virulence factors, including lipopolysaccharide (LPS) not only has been related with periodontitis but also with endothelial dysfunction, a key mechanism involved in the genesis of atherosclerosis and hypertension that involving systemic inflammatory markers as angiotensin II (Ang II) and cytokines. This study compares the effect of repeated and unique exposures of P. gingivalis W83 LPS and live bacteria on the production and expression of inflammatory mediators and vasoconstrictor molecules with Ang II. Human coronary artery endothelial cells (HCAEC) were stimulated with purified LPS of P. gingivalis (1.0, 3.5 or 7.0 µg/mL) or serial dilutions of live bacteria (MOI 1: 100 - 1:0,1) at a single or repeated exposure for a time of 24 h. mRNA expression levels of AGTR1, AGTR2, IL-8, IL-1ß and MCP-1 were determined by RT-qPCR, and IL-6, MCP-1, IL-8, IL-1ß and GM-CSF levels were measured by flow cytometry, ELISA determined Ang II levels. Live bacteria in a single dose increased mRNA levels of AGTR1, and repeated doses increased mRNA levels of IL-8 and IL-1ß (p < 0.05). Repeated exposure of live-P. gingivalis induced significant production IL-6, MCP-1 and GM-CSF (p < 0.05). Moreover, these MCP-1, IL-6 and GM-CSF levels were greater than in cells treated with single exposure (p < 0.05), The expression of AGTR1 and production of Ang II induced by live-P. gingivalis W83 showed a vasomotor effect of whole bacteria in HCAEC more than LPS. In conclusion, the findings of this study suggest that repeated exposure of P. gingivalis in HCAEC induces the activation of proinflammatory and vasoconstrictor molecules that lead to endothelial dysfunction being a key mechanism of the onset and progression of arterial hypertension and atherosclerosis.


Assuntos
Angiotensina II/metabolismo , Aterosclerose/metabolismo , Hipertensão/metabolismo , Periodontite/etiologia , Porphyromonas gingivalis/metabolismo , Angiotensina II/genética , Aterosclerose/microbiologia , Aterosclerose/patologia , Quimiocina CCL2/genética , Vasos Coronários/metabolismo , Vasos Coronários/microbiologia , Vasos Coronários/patologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/microbiologia , Citometria de Fluxo , Regulação da Expressão Gênica/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Humanos , Hipertensão/microbiologia , Hipertensão/patologia , Inflamação/genética , Inflamação/metabolismo , Inflamação/microbiologia , Inflamação/patologia , Interleucina-6/genética , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , Periodontite/genética , Periodontite/metabolismo , Periodontite/microbiologia , Porphyromonas gingivalis/patogenicidade , RNA Mensageiro/genética , Receptor Tipo 1 de Angiotensina/genética
14.
Int J Med Sci ; 16(10): 1320-1327, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692996

RESUMO

Porphyromonas gingivalis is a pivotal periodontal pathogen, and the epithelial cells serve as the first physical barrier to defend the host from bacterial attack. Within this host-bacteria interaction, P. gingivalis can modify the host immune reaction and adjust the gene expression, which is associated with periodontitis pathogenesis and developing strategies. Herein, a meta-analysis was made to get the differential gene expression profiles in epithelial cells with or without P. gingivalis infection. The network-based meta-analysis program for gene expression profiling was used. Both the gene ontology analysis and the pathway enrichment analysis of the differentially expressed genes were conducted. Our results determined that 290 genes were consistently up-regulated in P. gingivalis infected epithelial cells. 229 gene ontology biological process terms of up-regulated genes were discovered, including "negative regulation of apoptotic process" and "positive regulation of cell proliferation/migration/angiogenesis". In addition to the well-known inflammatory signaling pathways, the pathway associated with a transcriptional misregulation in cancer has also been increased. Our findings indicated that P. gingivalis benefited from the survival of epithelial cells, and got its success as a colonizer in oral epithelium. The results also suggested that infection of P. gingivalis might contribute to oral cancer through chronic inflammation. Negative regulation of the apoptotic process and transcriptional misregulation in cancer pathway are important contributors to the cellular physiology changes during infection development, which have particular relevance to the pathogenesis and progressions of periodontitis, even to the occurrence of oral cancer.


Assuntos
Infecções por Bacteroidaceae/imunologia , Interações Hospedeiro-Patógeno/genética , Neoplasias Bucais/patologia , Periodontite/imunologia , Porphyromonas gingivalis/imunologia , Infecções por Bacteroidaceae/genética , Infecções por Bacteroidaceae/microbiologia , Infecções por Bacteroidaceae/patologia , Sobrevivência Celular/genética , Sobrevivência Celular/imunologia , Progressão da Doença , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Perfilação da Expressão Gênica , Ontologia Genética , Gengiva/citologia , Gengiva/imunologia , Gengiva/microbiologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Mucosa Bucal/citologia , Mucosa Bucal/imunologia , Mucosa Bucal/microbiologia , Neoplasias Bucais/genética , Neoplasias Bucais/imunologia , Neoplasias Bucais/microbiologia , Periodontite/genética , Periodontite/microbiologia , Periodontite/patologia , Porphyromonas gingivalis/isolamento & purificação , Porphyromonas gingivalis/patogenicidade , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Regulação para Cima
15.
Acta Biochim Biophys Sin (Shanghai) ; 51(12): 1208-1215, 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31735958

RESUMO

Emerging evidence shows that the long noncoding RNA taurine-upregulated gene 1 (TUG1) plays pivotal roles in regulating biological properties and functions of parenchyma cells in various types of disease processes. However, the mechanism underlying the effects of TUG1 on cell proliferation and apoptosis of human periodontal ligament cells (PDLCs) in periodontitis is undefined. In this study, we explored the functions of TUG1 and its underlying mechanisms in the inflammatory process induced by Porphyromonas gingivalis-derived lipopolysaccharide (LPS) in PDLCs. Our results showed that TUG1 had a decreased expression in both periodontal ligament (PDL) tissues with periodontitis and PDLCs under a LPS-induced inflammatory condition, and TUG1 expression was negatively correlated with miR-132 expression in periodontitis-affected PDL tissues. Furthermore, we found that TUG1 overexpression in PDLCs alleviated LPS-induced proliferative inhibition and apoptosis promotion, while TUG1 knockdown had the opposite effect. In addition, miR-132 inhibitor alleviated TUG1 knockdown-induced inhibition of proliferation and increase of apoptosis in PDLCs under inflammatory conditions induced by LPS. These findings indicated that TUG1 has an enormous potential in regulating cell proliferation and apoptosis of PDLCs during periodontitis and may provide an effective therapeutic target for periodontitis to reduce the damage caused by inflammatory reactions.


Assuntos
Infecções por Bacteroidaceae/metabolismo , MicroRNAs/metabolismo , Ligamento Periodontal , Periodontite/metabolismo , RNA Longo não Codificante/fisiologia , Adulto , Apoptose , Proliferação de Células , Voluntários Saudáveis , Humanos , Lipopolissacarídeos , Ligamento Periodontal/metabolismo , Ligamento Periodontal/patologia , Porphyromonas gingivalis/patogenicidade , Adulto Jovem
16.
Int Immunopharmacol ; 77: 105956, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31655342

RESUMO

PURPOSE: To explore whether receptor activator of nuclear factor kappa-B ligand (RANKL) is involved in the nosogenesis of peri-implantitis and to reveal the regulatory mechanism in Porphyromonas gingivalis induced RANKL production. METHODS: Therefore, we collected peri-implant crevicular fluid (PICF) and gingival tissues from healthy implants and peri-implantitis patients. The expression of RANKL in samples was tested by ELISA, Western blot and immunofluorescence staining. The production of RANKL in THP-1 macrophages stimulated with P. gingivalis was detected by qRT-PCR and Western blot. Then macrophages were pre-treated with neutralizing antibodies of Toll-like receptor 2 (TLR2) or lectin-type oxidized LDL receptor 1 (LOX-1) and inhibitors of TLR2, LOX-1 or Erk1/2 before P. gingivalis stimulation to evaluate the roles of TLR2, LOX-1 and Erk1/2 in RANKL production by qRT-PCR and Western blot. RESULTS: The protein level of RANKL was higher in PICF of peri-implantitis patients than healthy implants. We observed increased RANKL expression in P. gingivalis infected macrophages compared to controls. RANKL induced by P. gingivalis stimulation was mediated by TLR2 and Erk1/2 signaling pathway in THP-1 macrophages. LOX-1 is involved in TLR2 induced RANKL expression. CONCLUSION: RANKL was involved in peri-implantitis, and regulated by TLR2, LOX-1 and Erk1/2 signaling against P. gingivalis infection. As the novel inflammation pathway triggers, TLR2 and LOX-1 which mediate RANKL production seems to be potential drug targets of peri-implantitis.


Assuntos
Peri-Implantite/metabolismo , Ligante RANK/metabolismo , Receptores Depuradores Classe E/metabolismo , Receptor 2 Toll-Like/metabolismo , Linhagem Celular , Citocinas/metabolismo , Implantes Dentários/microbiologia , Humanos , Inflamação/metabolismo , Macrófagos/metabolismo , Porphyromonas gingivalis/patogenicidade , Células THP-1
17.
Nutrients ; 11(9)2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31527555

RESUMO

BACKGROUND: Coffee is a major dietary source of polyphenols. Previous research found that coffee had a protective effect on periodontal disease. In this study, we aimed to investigate whether coffee extract and its primary phenolic acid, chlorogenic acid, affect the growth and protease activity of a periodontopathogen Porphyromonas gingivalis (P. gingivalis). METHODS: Coffee extract and chlorogenic acid were prepared by a two-fold serial dilution. The turbid metric test and plate count method were used to examine the inhibitory effects of chlorogenic acid on P. gingivalis. The time-kill assay was used to measure changes in the viability of P. gingivalis after exposure to chlorogenic acid for 0-24 h. The protease activity of P. gingivalis was analyzed using the optical density of a chromogenic substrate. RESULTS: As a result, the minimum inhibitory concentration (MIC) of chlorogenic acid was 4 mg/mL, and the minimum bactericidal concentration was 16 mg/mL. Chlorogenic acid at concentrations above MIC resulted in a longer-lasting inhibitory effect on P. gingivalis viability and significantly reduced associated protease activity. The coffee extract showed antibacterial activity as observed by the disk diffusion test, whereas these inhibitory effects were not affected by different roast degrees of coffee. CONCLUSIONS: Collectively, our novel findings indicate that chlorogenic acid not only has antimicrobial activity but also reduced the protease activity of P. gingivalis. In addition, coffee extract inhibits the proliferation of P. gingivalis, which may partly be attributed to the effect of chlorogenic acid.


Assuntos
Antibacterianos/farmacologia , Infecções por Bacteroidaceae/prevenção & controle , Ácido Clorogênico/farmacologia , Coffea/química , Periodontite/tratamento farmacológico , Extratos Vegetais/farmacologia , Porphyromonas gingivalis/efeitos dos fármacos , Antibacterianos/isolamento & purificação , Proteínas de Bactérias/metabolismo , Infecções por Bacteroidaceae/microbiologia , Ácido Clorogênico/isolamento & purificação , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Viabilidade Microbiana/efeitos dos fármacos , Peptídeo Hidrolases/metabolismo , Periodontite/microbiologia , Extratos Vegetais/isolamento & purificação , Porphyromonas gingivalis/enzimologia , Porphyromonas gingivalis/patogenicidade , Sementes/química , Fatores de Tempo , Fatores de Virulência/metabolismo
18.
Microbiology (Reading) ; 165(11): 1181-1197, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31517596

RESUMO

Key to onset and progression of periodontitis is a complex relationship between oral bacteria and the host. The organisms most associated with severe periodontitis are the periodontal pathogens of the red complex: Tannerella forsythia, Treponema denticola and Porphyromonas gingivalis. These organisms express sialidases, which cleave sialic acid from host glycoproteins, and contribute to disease through various mechanisms. Here, we expressed and purified recombinant P. gingivalis sialidase SiaPG (PG_0352) and characterized its activity on a number of substrates, including host sialoglycoproteins and highlighting the inability to cleave diacetylated sialic acids - a phenomenon overcome by the NanS sialate-esterase from T. forsythia. Indeed SiaPG required NanS to maximize sialic acid harvesting from heavily O-acetylated substrates such as bovine salivary mucin, hinting at the possibility of interspecies cooperation in sialic acid release from host sources by these members of the oral microbiota. Activity of SiaPG and P. gingivalis was inhibited using the commercially available chemotherapeutic zanamivir, indicating its potential as a virulence inhibitor, which also inhibited sialic acid release from mucin, and was capable of inhibiting biofilm formation of P. gingivalis on oral glycoprotein sources. Zanamivir also inhibited attachment and invasion of oral epithelial cells by P. gingivalis and other periodontal pathogens, both in monospecies but also in multispecies infection experiments, indicating potential to suppress host-pathogen interactions of a mixed microbial community. This study broadens our understanding of the multifarious roles of bacterial sialidases in virulence, and indicates that their inhibition with chemotherapeutics could be a promising strategy for periodontitis therapy.


Assuntos
Proteínas de Bactérias/metabolismo , Interações Hospedeiro-Patógeno , Neuraminidase/metabolismo , Porphyromonas gingivalis/enzimologia , Fatores de Virulência/metabolismo , Proteínas de Bactérias/genética , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Linhagem Celular , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Interações Microbianas , Mucinas/metabolismo , Mutação , Neuraminidase/genética , Polissacarídeos/metabolismo , Porphyromonas gingivalis/efeitos dos fármacos , Porphyromonas gingivalis/crescimento & desenvolvimento , Porphyromonas gingivalis/patogenicidade , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Sialoglicoproteínas/metabolismo , Tannerella forsythia/enzimologia , Fatores de Virulência/genética , Zanamivir/farmacologia
19.
Technol Cancer Res Treat ; 18: 1533033819867354, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31370775

RESUMO

Despite advancement in cancer treatment, oral cancer has a poor prognosis and is often detected at late stage. To overcome these challenges, investigators should search for early diagnostic and prognostic biomarkers. More than 700 bacterial species reside in the oral cavity. The oral microbiome population varies by saliva and different habitats of oral cavity. Tobacco, alcohol, and betel nut, which are causative factors of oral cancer, may alter the oral microbiome composition. Both pathogenic and commensal strains of bacteria have significantly contributed to oral cancer. Numerous bacterial species in the oral cavity are involved in chronic inflammation that lead to development of oral carcinogenesis. Bacterial products and its metabolic by-products may induce permanent genetic alterations in epithelial cells of the host that drive proliferation and/or survival of epithelial cells. Porphyromonas gingivalis and Fusobacterium nucleatum induce production of inflammatory cytokines, cell proliferation, and inhibition of apoptosis, cellular invasion, and migration thorough host cell genomic alterations. Recent advancement in metagenomic technologies may be useful in identifying oral cancer-related microbiome, their genomes, virulence properties, and their interaction with host immunity. It is very important to address which bacterial species is responsible for driving oral carcinogenesis. Alteration in the oral commensal microbial communities have potential application as a diagnostic tool to predict oral squamous cell carcinoma. Clinicians should be aware that the protective properties of the resident microflora are beneficial to define treatment strategies. To develop highly precise and effective therapeutic approaches, identification of specific oral microbiomes may be required. In this review, we narrate the role of microbiome in the progression of oral cancer and its role as an early diagnostic and prognostic biomarker for oral cancer.


Assuntos
Carcinogênese/genética , Inflamação/microbiologia , Microbiota/genética , Neoplasias Bucais/microbiologia , Carcinogênese/patologia , Proliferação de Células/genética , Fusobacterium nucleatum/patogenicidade , Humanos , Inflamação/genética , Inflamação/patologia , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Porphyromonas gingivalis/patogenicidade , Prognóstico , Saliva/microbiologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-31380305

RESUMO

Periodontitis is a common intraoral infection and is inextricably linked to systemic diseases. Recently, the regulation between host immunologic response and periodontal pathogens has become a hotspot to explain the mechanism of periodontitis and related systemic diseases. Since Porphyromonas gingivalis (P. gingivalis) was proved as critical periodontal pathogen above all, researches focusing on the mechanism of its virulence factors have received extensive attention. Studies have shown that in the development of periodontitis, in addition to the direct release of virulent factors by periodontal pathogens to destroy periodontal tissues, over-low or over-high intrinsic immune and inflammatory response mediated by Toll-like receptors (TLRs) can lead to more lasting destruction of periodontal tissues. It is very necessary to sort out how various cytopathic factors of P. gingivalis mediate inflammation and immune responses between the host through TLRs so as to help precisely prevent, diagnose, and treat periodontitis in clinic. This review summarizes the role of three most widely studied pathogenic factors produced by P. gingivalis (lipopolysaccharide, gingipains, pili) and their interactions with TLRs at the cellular and molecular level in the progress of periodontitis.


Assuntos
Fímbrias Bacterianas/metabolismo , Cisteína Endopeptidases Gingipaínas/metabolismo , Interações Hospedeiro-Patógeno , Lipopolissacarídeos/metabolismo , Porphyromonas gingivalis/patogenicidade , Receptores Toll-Like/metabolismo , Fatores de Virulência/metabolismo , Animais , Infecções por Bacteroidaceae/microbiologia , Infecções por Bacteroidaceae/patologia , Infecções por Bacteroidaceae/fisiopatologia , Modelos Animais de Doenças , Humanos , Periodontite/microbiologia , Periodontite/patologia , Periodontite/fisiopatologia
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