RESUMO
sTREM-1 and its ligand PGLYRP1 play an essential role in the inflammatory process around teeth and implants. In this study, we aimed to evaluate the impact of peri-implant treatment on the salivary levels of the sTREM-1/PGLYRP-1/MMP-8 axis after 3 months. A total of 42 participants (with a mean age of 61 years old ± 7.3) were enrolled in this longitudinal study, 24 having peri-implant mucositis (MU) and 18 having peri-implantitis (PI). Clinical peri-implant parameters, such as probing pocket depth (PPD), % of plaque, and bleeding on probing (BOP), and the whole unstimulated saliva samples were evaluated at baseline and 3 months after treatment. The MU group received nonsurgical peri-implant treatment, while the PI group received open-flap procedures. The levels of sTREM-1, PGLYRP-1, MMP-8, and TIMP-1 were analyzed using enzyme-linked immunosorbent assays. BOP, plaque levels, and PPD significantly reduced after treatment in both groups. A significant decrease in the salivary levels of sTREM-1, MMP-8, and TIMP-1 in the PI group and PGLYRP1 and TIMP-1 in the MU group were observed. Salivary levels of sTREM-1 were significantly reduced in patients with PI but not with MU. Additionally, peri-implant treatment had a significantly higher impact on MMP-8 reduction in patients with PI than in those with MU.
Assuntos
Metaloproteinase 8 da Matriz , Peri-Implantite , Receptor Gatilho 1 Expresso em Células Mieloides , Idoso , Humanos , Estudos Longitudinais , Metaloproteinase 8 da Matriz/genética , Pessoa de Meia-Idade , Peri-Implantite/metabolismo , Peri-Implantite/cirurgia , Estudos Prospectivos , Inibidor Tecidual de Metaloproteinase-1/genética , Receptor Gatilho 1 Expresso em Células Mieloides/genéticaRESUMO
Uncontrolled inflammatory responses play a critical role in coronavirus disease (COVID-19). In this context, because the triggering-receptor expressed on myeloid cells-1 (TREM-1) is considered an intrinsic amplifier of inflammatory signals, this study investigated the role of soluble TREM-1 (sTREM-1) as a biomarker of the severity and mortality of COVID-19. Based on their clinical scores, we enrolled COVID-19 positive patients (n = 237) classified into mild, moderate, severe, and critical groups. Clinical data and patient characteristics were obtained from medical records, and their plasma inflammatory mediator profiles were evaluated with immunoassays. Plasma levels of sTREM-1 were significantly higher among patients with severe disease compared to all other groups. Additionally, levels of sTREM-1 showed a significant positive correlation with other inflammatory parameters, such as IL-6, IL-10, IL-8, and neutrophil counts, and a significant negative correlation was observed with lymphocyte counts. Most interestingly, sTREM-1 was found to be a strong predictive biomarker of the severity of COVID-19 and was related to the worst outcome and death. Systemic levels of sTREM-1 were significantly correlated with the expression of matrix metalloproteinases (MMP)-8, which can release TREM-1 from the surface of peripheral blood cells. Our findings indicated that quantification of sTREM-1 could be used as a predictive tool for disease outcome, thus improving the timing of clinical and pharmacological interventions in patients with COVID-19.
Assuntos
Biomarcadores/sangue , COVID-19/diagnóstico , COVID-19/mortalidade , Leucócitos/metabolismo , Metaloproteinase 8 da Matriz/metabolismo , Índice de Gravidade de Doença , Receptor Gatilho 1 Expresso em Células Mieloides/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Feminino , Humanos , Inflamação , Interleucina-10/sangue , Interleucina-6/sangue , Interleucina-8/sangue , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Estudos Prospectivos , SARS-CoV-2 , Receptor Gatilho 1 Expresso em Células Mieloides/metabolismo , Adulto JovemRESUMO
OBJECTIVES: The aim of this study is to investigate the expression of sTREM-1 and its ligand PGLYRP1, as well as the expression of MMP-8 and its inhibitor TIMP-1, in peri-implant diseases. As a secondary aim, we analyzed the influence of the concomitant existence of periodontitis in the expression of these biomarkers. MATERIALS AND METHODS: This study included 77 patients (29 males and 48 females; mean age 55.0 ± 11.5), 18 having gingivitis, 16 having periodontitis, 20 having mucositis, and 23 having peri-implantitis. Patients were clinically examined, and unstimulated whole saliva was collected. sTREM-1, PGLYRP1, MMP-8, TIMP-1, and MMP-8/TIMP1 ratio were determined by ELISA. RESULTS: The periodontitis group presented higher probing depth (PD) mean, and higher clinical attachment loss, compared with the other groups. The peri-implantitis group presented higher PD mean in implants compared to the mucositis group. Patients with PD ≥ 6 mm showed significantly higher levels of PGLYRP1, MMP-8, and MMP-8/TIMP-1 ratio than patients with PD < 6 mm. When all four markers were assessed, there were no significant differences between mucositis and peri-implantitis groups. Concomitant periodontitis resulted in higher significant levels of MMP-8 in patients with peri-implant disease. CONCLUSION: We did not observe significant differences in the levels of the sTREM-1/PGLYRP1/MMP-8 axis between patients with periodontal and peri-implant diseases, suggesting that these markers are also involved in the inflammatory process around implants. Besides, the presence of periodontitis may affect the levels of MMP-8 in patients with peri-implant disease. CLINICAL RELEVANCE: The sTREM-1/PGLYRP1/MMP-8 axis could be useful as potent markers in periodontal and peri-implant diseases.
Assuntos
Citocinas/metabolismo , Implantes Dentários , Metaloproteinase 8 da Matriz/metabolismo , Peri-Implantite/metabolismo , Periodontite/metabolismo , Receptor Gatilho 1 Expresso em Células Mieloides/metabolismo , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidor Tecidual de Metaloproteinase-1/metabolismoRESUMO
O objetivo desse estudo clínico randomizado foi avaliar em dentes com infecção endodôntica primária (IEP) os microrganismos anaeróbios cultiváveis (UFC/mL), níveis de endotoxinas (LPS) (EU/mL) e colagenase/MMP-8 da região periapical antes e durante o tratamento endodôntico utilizando diferentes protocolos de irrigação final: irrigação convencional (CNI), ativação ultrassônica passiva (PUA) e ativação ultrassônica continua (CUA). Quarenta e cinco dentes com IEP foram submetidos ao tratamento endodôntico utilizando NaOCl 2.5% como solução irrigadora seguido do uso de EDTA 17%. Os protocolos de limpeza final foram realizados com irrigação com agulha convencional (controle), PUA e CUA; na sequência os canais foram preenchidos com pasta de Ca(OH)2 + SS por 14 dias. Foram feitas coletas do conteúdo do canal radicular após abertura coronária (S1), após diferentes protocolos de irrigação final (S2) e após uso de medicação intracanal com pasta de hidróxido de cálcio [Ca(OH)2] (S3). O conteúdo coletado do canal foi submetido as análises por cultura microbiológica (UFC/mL) e níveis de endotoxinas (EU/mL) pelo Lisado de Amebócitos de Limulus (LAL). Após preparo dos canais e após medicação com Ca(OH)2 foram realizadas coletas do fluido periapical para análise da expressão de MMP-8 por ELISA. A análise estatística dos dados foi realizada pelo testes Kruskal-Wallis e Dunn para analise intergrupos de UFC/mL, LPS e MMP-8, todos eles com nível de significância de 5% (P<0.05). Microrganismos anaeróbios cultiváveis foram detectados em 100 % das amostras iniciais (S1) com valor médio de 1.18 x 105 CFU/mL (20 1.84 x 106 CFU/mL). CUA apresentou maior efetividade na redução de microrganismos anaeróbios cultiváveis em S3 (97.27%) seguido pela PUA (96.56%) e CNI (96.2%). Endotoxinas foram identificadas em 100% das amostras em S1 com valor médio de 538.10 EU/mL (0.017 x 6190 EU/mL), CUA mostrou uma maior redução nos níveis de LPS em S3 (97.75 %), seguido pela PUA (97.11%) e CNI (90.42%). O protocolo de irrigação final com ativação ultrassônica PUA e CUA favoreceu a redução de MMP-8 em comparação ao grupo CNI. Houve correlação estatística positiva entre os níveis de LPS e MMP-8. Conclui-se que o preparo biomecânico produz a maior redução no número de microrganismos anaeróbios e endotoxinas; O protocolo de irrigação final com PUA e CUA em associação ao preparo biomecânico produz maior redução nos níveis de Endotoxinas e MMP-8 em comparação com CNI. Existe correlação estatística positiva entre os níveis de LPS e MMP-8 presentes nas infecções endodônticas primárias, mostrando a associação do LPS com o processo de destruição tecidual(AU)
The aim of this randomized clinical trial was to evaluate in cultivated anaerobic microorganisms (CFU / mL), endotoxin levels (LPS) (EU / mL) and periapical collagenase / MMP-8 in teeth with primary endodontic infection (EPI) before and during Endodontic treatment using different final irrigation protocols: conventional irrigation (CNI), passive ultrasonic activation (PUA) and continuous ultrasonic activation (CUA). Forty-five teeth with IEP were submitted to endodontic treatment using 2.5% NaOCl as an irrigating solution followed by 17% EDTA. Final cleaning protocols were performed with conventional needle irrigation (control), PUA and CUA; The root canals were then filled with Ca (OH)2 paste for 14 days. Root canal contents were collected after coronary opening (S1), after root canal preparation (S2) and after intracanal calcium hydroxide paste [Ca (OH)2] (S3). Samples of the root canal content was performed to analysis by microbiological culture (CFU / mL) and endotoxin levels (EU / mL) by Limulus Amebocyte Lysate (LAL). After canal preparation and after Ca (OH)2 medication, periapical fluid samples were collected for analysis of MMP-8 expression by ELISA. Statistical analysis of the data was performed by Kruskal-Wallis and Dunn tests for intergroup analysis of CFU / mL, LPS and MMP-8, all with a significance level of 5% (P <0.05). Cultivable anaerobic microorganisms were detected in 100% of the initial samples (S1) with a mean value of 1.18 x 105 CFU / mL (20 - 1.84 x 106 CFU / mL). CUA showed greater effectiveness in reducing anaerobic microorganisms cultivable in S3 (97.27%) followed by PUA (96.56%) and CNI (96.2%). Endotoxins were identified in 100% of samples in S1 with a mean value of 538.10 EU / mL (0.017 x 6190 EU / mL), CUA showed a greater reduction in LPS levels in S3 (97.75%), followed by PUA (97.11%). and CNI (90.42%). The final irrigation protocol with ultrasonic activation PUA and CUA favored the reduction of MMP-8 compared to the CNI group. There was a positive statistical correlation between LPS and MMP-8 levels. It is concluded that the biomechanical preparation produces the greater reduction in the number of anaerobic microorganisms and endotoxins; The final irrigation protocol with PUA and CUA in combination with biomechanical preparation produces greater reduction in Endotoxin and MMP-8 levels compared to CNI. There is a positive statistical correlation between the levels of LPS and MMP-8 present in primary endodontic infections, showing the association of LPS with the tissue destruction process(AU)
Assuntos
Endotoxinas , Controle de InfecçõesRESUMO
PROBLEM: A wide variety of mediators are involved in inflammatory processes. However, the identity of those participating in vaginal immune responses has not been established. We correlated extracellular matrix metalloproteinase inducer (EMMPRIN), matrix metalloproteinase-8 (MMP-8), hyaluronan (HA), hyaluronidase-1 (Hyal-1), human ß-defensin-2 (hBD2), and neutrophil gelatinase-associated lipocalin (NGAL) concentrations with the extent of leukocyte infiltration into the vagina and suggest their participation in vaginal inflammation. METHODS OF STUDY: Vaginal fluid was obtained from 233 women seen at the outpatient clinic in the Department of Obstetrics and Gynecology at Campinas University, Brazil. The magnitude of vaginal inflammation was determined by the leukocyte count on vaginal smears and categorized as no inflammation (0 leukocytes/field), moderate inflammation (1-4 leukocytes/field), and intense inflammation (>4 leukocytes/field). Concentrations of EMMPRIN, MMP-8, HA, Hyal-1, hBD2, and NGAL were determined in vaginal fluid by ELISA. RESULTS: EMMPRIN, MMP-8, HA, hBD2, and NGAL concentration increased with elevated leukocyte numbers (P < 0.05), while Hyal-1 did not. EMMPRIN concentrations were correlated with HA and MMP-8 levels. CONCLUSION: EMMPRIN, MMP-8, HA, ß-defensin, and NGAL are elevated in women with vaginal inflammation.
Assuntos
Proteínas de Fase Aguda/imunologia , Basigina/imunologia , Ácido Hialurônico/imunologia , Lipocalinas/imunologia , Metaloproteinase 8 da Matriz/imunologia , Proteínas Proto-Oncogênicas/imunologia , Vaginite/imunologia , beta-Defensinas/imunologia , Adulto , Feminino , Humanos , Hialuronoglucosaminidase/imunologia , Leucócitos/imunologia , Lipocalina-2 , Adulto JovemRESUMO
Posterior tibial tendon is particularly vulnerable and is responsible for much morbidity in sportspersons. Some patients have a predisposition without a clinically recognized cause, suggesting that individual characteristics, inclusive genetic inheritance, play an important role in tendinopathy. Matrix metalloproteinase (MMP)-8 is a proteinase capable of degrading a large amount of extracellular proteins, and influence degradation and remodeling of collagen. To determine whether the -799 polymorphism in the promoter of MMP-8 gene is associated with tendinopathy in posterior tibial tendon, 50 patients undergoing surgical procedures and anatomopathological diagnosis of degenerative lesions of the posterior tibial tendon and 100 control patients with posterior tibial tendon integrity and without signs of degeneration in magnetic resonance imaging were evaluated for the -799 MMP-8 polymorphism. There was a significant difference in the presence of the different alleles (P = 0.001) and genotype (P = 0.003) between the control group and the test group for the MMP-8 gene. The polymorphism at position -799 of the gene for MMP-8 is associated with tendinopathy primary posterior tibial tendon in the population studied. The results suggest that individuals with the T allele are at greater risk of developing tendinopathy.
Assuntos
Metaloproteinase 8 da Matriz/genética , Disfunção do Tendão Tibial Posterior/genética , Regiões Promotoras Genéticas/genética , Tendinopatia/genética , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Pessoa de Meia-Idade , Polimorfismo GenéticoRESUMO
En la periodontitis crónica (PC) se desencadenan procesos inmunoinflamatorios, donde se liberan metaloproteinasas de la matriz (MMPs), enzimas involucradas en la degradación de la matriz extracelular, las cuales pueden ser detectadas en el fluido gingival crevicular (FGC). El propósito del estudio fue determinar los niveles de MMP-3 y MMP-8 en FGC, antes y después del tratamiento periodontal no quirúrgico (TPNQ) para evaluar actividad de la enfermedad y respuesta terapéutica. Once pacientes con periodontitis crónica y 11 controles sanos fueron seleccionados. Se evaluaron los parámetros clínicos: índice gingival, índice de placa, profundidad al sondaje y pérdida de inserción; en todos los dientes de cada individuo y en seis sitios por diente. Muestras de FGC fueron tomadas de un diente por cuadrante, con profundidad de saco ≥ 4mm y pérdida de inserción ≥ 5 mm, los niveles de MMP-3 y MMP-8 fueron determinados por ELISA. Diferencias estadísticamente significativas fueron observadas entre los parámetros clínicos del grupo control y los pacientes con PC antes del tratamiento, registrándose posterior al TPNQ disminución significativa de todos los índices. Las concentraciones iniciales de MMP-3 y 8 en el grupo con PC fueron significativamente mayores a las obtenidas luego del TPNQ y en el grupo control, sin observar correlación entre parámetros clínicos y niveles de MMPs. La disminución significativa de los valores de MMP-3 y 8 en FGC de los pacientes con PC, posterior al TPNQ, indican la participación importante de estas enzimas en la degradación del tejido, y la efectividad del tratamiento periodontal para su control.
Immune-inflammatory processes are trigged in chronic periodontitis (CP), where matrix metalloproteinases (MMPs) are released and involved in the degradation of the extracellular matrix components that can be detected in the gingival crevicular fluid (GCF). The purpose of the study was to determine the levels of MMP-3 and MMP-8 in GCF, before and after nonsurgical periodontal treatment (NSPT), to evaluate disease activity and therapy response. Eleven patients with PC and eleven healthy controls were selected. Clinical measurements to evaluate gingival index (GI), plaque index (PI), probing depth (PD) and clinical attachment loss (CAL) were made in all the teeth of each individual and in six sites per tooth. GCF samples were taken from one tooth per quadrant, with a pocket depth ≥ 4 mm and a clinical attachment loss ≥ 5 mm, and the levels of MMP-3 and MMP-8 measured using an ELISA test. Statistically significant differences in clinical parameters were observed (p < 0.05) between patients with CP and control groups before the periodontal treatment, with significant decrease in all indexes after the NSPT. The initial concentrations of MMP-3 and MMP-8 were significantly higher than those obtained after the NSPT and in the control group, without observing a correlation between the clinical parameters and the levels of MMPs. Increased levels of MMP-3 and MMP-8 in the GCF of patients with PC declined significantly after NSPT, and the difference between the levels in healthy individuals and patients, suggests the important participation of these MMPs in tissue destruction in PC disease.
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Líquido do Sulco Gengival/enzimologia , /análise , /análise , Periodontite/enzimologia , Biomarcadores , Doença Crônica , Ensaio de Imunoadsorção Enzimática , Índice Periodontal , Periodontite/terapiaRESUMO
As metaloproteinases da matriz (MMP) e os inibidores de metaloproteinase da matriz (TIMP) são enzimas extremamente importantes na remodelação do tecido conjuntivo durante o desenvolvimento, homeostase e cicatrização. O desequilibrio entre as MMPs ativadas e seus inibidores endógenos leva ao colapso patológico da matriz extracelular durante a doença periodontal provocando a degradação das fibras colágenas inseridas na raiz e a migração apical do epitélio com formação da bolsa periodontal. A MMP-8 destaca-se entre as MMPs predominantemente presentes no tecido gengival inflamado, fluido gengival crevicular e saliva bem como fluido sulcular e peri-implantar. O nível e grau de ativação desta enzima parecem aumentar com o aumento da atividade e gravidade da doença periodontal e diminuir em seguida ao tratamento. Diante da importância dessa enzima na evolução da doença periodontal, esse trabalho teve como objetivo desenvolver uma revisão de literatura sobre o papel da MMP- 8 e do seu principal inibidor, TIMP-1, na degradação de colágeno gengival durante a doença periodontal, destacando suas características, mecanismo de ação e inibição, expressão tecidual e níveis no fluido gengival crevicular.
Matrix metaloproteinase (MMP) and tissue inhibitor of matrix metalloproteinase (TIMP) are extremely important enzymes in connective tissue remodeling during development, homeostasis and healing. An imbalancebetween active MMPs and TIMPs create a pathological collapse of extracellular matrix during periodontal disease generating degradation of collagen fibers attached to the root surface and epithelial apical migration with pocket formation. MMP-8 is the major class among MMPs observed in inflammed gingival tissue, gingival crevicular fluid, saliva as well as dental and peri-implantar sulcular fluid. The levels and activation of this enzyme seems to increase with the activity and severity of periodontal disease, and decrease after treatment. Due to MMP-8 relevance in periodontal disease development, this paper aimed to review MMP-8 and TIMP-1 participation in gingival collagen degradation during periodontal disease, underlining the enzyme characteristics, action and inhibition mechanisms, tissular expression and gingival crevicular fluid levels.