RESUMO
The hypothesis that physiological changes in women can affect periodontal tissues is the subject of this study, and inflammatory markers such as matrix metalloproteinase-8 can measure susceptibility to inflammation. The study aimed to analyze MMP-8 levels in periodontal sites of postpartum women and women without a history of pregnancy, comparing health parameters and periodontal disease. This is a case-control study with 40 participants, 20 cases (women in the postpartum period) and 20 controls (women without any pregnancy), who underwent clinical periodontal examination and the collection of crevicular gingival fluid. The ELISA test was used to detect MMP-8 levels. Postpartum women had worse periodontal parameters, such as bleeding index on probing, number of sites with CAL ≥ 3, and fewer teeth present. In the group of women without a history of pregnancy, a significantly lower MMP-8 level was observed in healthy sites and a higher one was observed in periodontal pockets (p < 0.01). In contrast, in postpartum women, MMP-8 levels were elevated in both healthy sites and periodontal pockets (p > 0.01). The MMP-8 levels in gingival fluid appear to be related to periodontal clinical parameters and may be a possible marker of enzymatic changes involved in periodontal tissue destruction in postpartum women.
Assuntos
Líquido do Sulco Gengival , Metaloproteinase 8 da Matriz , Período Pós-Parto , Humanos , Feminino , Metaloproteinase 8 da Matriz/metabolismo , Metaloproteinase 8 da Matriz/análise , Adulto , Estudos de Casos e Controles , Líquido do Sulco Gengival/enzimologia , Gravidez , Doenças Periodontais/enzimologia , Biomarcadores/metabolismo , Adulto JovemRESUMO
Patients with COVID-19 predominantly have a respiratory tract infection and acute lung failure is the most severe complication. While the molecular basis of SARS-CoV-2 immunopathology is still unknown, it is well established that lung infection is associated with hyper-inflammation and tissue damage. Matrix metalloproteinases (MMPs) contribute to tissue destruction in many pathological situations, and the activity of MMPs in the lung leads to the release of bioactive mediators with inflammatory properties. We sought to characterize a scenario in which MMPs could influence the lung pathogenesis of COVID-19. Although we observed high diversity of MMPs in lung tissue from COVID-19 patients by proteomics, we specified the expression and enzyme activity of MMP-2 in tracheal-aspirate fluid (TAF) samples from intubated COVID-19 and non-COVID-19 patients. Moreover, the expression of MMP-8 was positively correlated with MMP-2 levels and possible shedding of the immunosuppression mediator sHLA-G and sTREM-1. Together, overexpression of the MMP-2/MMP-8 axis, in addition to neutrophil infiltration and products, such as reactive oxygen species (ROS), increased lipid peroxidation that could promote intensive destruction of lung tissue in severe COVID-19. Thus, the inhibition of MMPs can be a novel target and promising treatment strategy in severe COVID-19.
Assuntos
COVID-19 , Metaloproteinase 2 da Matriz , Antígenos HLA-G , Humanos , Imunidade , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 8 da Matriz/metabolismo , Estresse Oxidativo , SARS-CoV-2RESUMO
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
OBJECTIVE: In utero fetal surgery to correct incomplete closure of the spinal cord lessens the extent of permanent damage but is associated with preterm prelabour rupture of membranes (PPROM). We determined whether compounds in amniotic fluid collected at the time of surgery predicted subsequent development of PPROM. DESIGN: Prospective study. SETTING: Hospitals in Sao Paulo, Brazil. POPULATION: Twenty-four consecutive pregnant women at 24-26 weeks of gestation seen between February and October 2017 with a singleton pregnancy underwent in utero surgery to correct an open spinal defect in their fetus. METHODS: Amniotic fluid was tested for lactic acid, matrix metalloproteinase 2 (MMP-2), MMP-8, MMP-9 and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay. Clinical data were collected after completion of all laboratory studies. MAIN OUTCOME MEASURE: Amniotic fluid concentration of compounds in women with or without PPROM. RESULTS: Preterm prelabour rupture of membranes occurred in seven (29.2%) women. There were no differences in maternal age, gravidity, parity, race, history of caesarean sections or fetal gender between women with or without PPROM. Length of surgery, days of wound healing and length of hospital stay were also indistinguishable. The median concentrations of MMP-8 (1.7 versus 0.6 ng/ml; P = 0.0041) and lactic acid (7.1 versus 5.9 mm; P = 0.0181) were higher in women with PPROM. The amniotic fluid MMP-8 level was also negatively correlated with gestational age at delivery (Spearman r = -0.4217, P = 0.0319). CONCLUSION: Differences in susceptibility to develop PPROM are present before fetal surgery. An increase in anaerobic glycolysis, evidenced by the intra-amniotic lactic acid level, may enhance MMP-8 production and weaken maternal and fetal membranes. TWEETABLE ABSTRACT: Matrix metalloproteinase-8 and lactic acid in amniotic fluid predict preterm prelabour rupture of membranes.
Assuntos
Líquido Amniótico/metabolismo , Ruptura Prematura de Membranas Fetais/metabolismo , Ácido Láctico/metabolismo , Metaloproteinase 8 da Matriz/metabolismo , Coluna Vertebral/cirurgia , Biomarcadores/metabolismo , Feminino , Terapias Fetais , Idade Gestacional , Humanos , Interleucina-6/metabolismo , Projetos Piloto , Gravidez , Estudos Prospectivos , Coluna Vertebral/anormalidadesRESUMO
Periodontal disease is characterized as a disorder of the oral microbiota resulting in an immune response which, in turn, leads to the destruction of periodontal tissue. Matrix metalloproteinase-8 (MMP-8) has been reported as the major metalloproteinase involved in periodontal disease, being present at high levels in gingival crevicular fluid and salivary fluid (SF). The aim of this systematic review was to evaluate the scientific literature regarding the expression of MMP-8 in gingival crevicular fluid and SF in patients with periodontal disease, analyzing its validity as a possible biomarker in the diagnosis of periodontal disease. A systematic review of the literature was performed using the PubMed/Medline, CENTRAL and Science Direct databases. Studies concerning the use of MMP-8 in the diagnosis of periodontal disease that evaluated its effectiveness as a biomarker for periodontal disease were selected. The search strategy provided a total of 6483 studies. After selection, six articles met all the inclusion criteria and were included in the present systematic review. The studies demonstrated significantly higher concentrations of MMP-8 in patients with periodontal disease compared with controls, as well as in patients presenting more advanced stages of periodontal disease. The findings on higher MMP-8 concentrations in patients with periodontal disease compared with controls imply the potential adjunctive use of MMP-8 in the diagnosis of periodontal disease.
Assuntos
Biomarcadores , Metaloproteinase 8 da Matriz/análise , Metaloproteinase 8 da Matriz/metabolismo , Doenças Periodontais/diagnóstico , Doenças Periodontais/imunologia , Fatores Etários , Bases de Dados Factuais , Índice de Placa Dentária , Líquido do Sulco Gengival/imunologia , Gengivite/diagnóstico , Gengivite/imunologia , Humanos , Perda da Inserção Periodontal , Índice Periodontal , Bolsa Periodontal , Periodontite/diagnóstico , Periodontite/imunologia , Saliva/imunologia , Fatores SexuaisRESUMO
Background:Neisseria gonorrhoeae (Ngo) is the etiological agent of gonorrhea, a sexually transmitted infection that initially infects the female lower genital tract. In untreated women, the bacteria can ascend to the upper genital reproductive tract and infect the fallopian tube (FTs), which is associated with salpingitis and can lead to impaired FT function and infertility. The extracellular matrix (ECM) plays an important role in cell migration and differentiation in the female genital tract, and some pathogens modify the ECM to establish successful infections. The ECM is regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), their endogenous inhibitors; MMP deregulation causes pathological conditions in a variety of tissues. Results: The aim of this work was to analyze the expression and localization of MMP-3, MMP-8, MMP-9, and TIMP-1 in FT explants during Ngo infection using real-time PCR, immunohistochemistry, zymography and ELISA. No significant variations in MMP-3, MMP-9, and TIMP-1 transcript levels were observed. In contrast, a significant increase (p < 0.05) was observed for MMP-8 expression and was accompanied by stromal immunoreactivity in infected explants. ELISA results supported these findings and showed that MMP-8 release increased upon gonococcal infection. Conclusions: Our results indicate that gonococcal infection induces increased MMP-8 expression, which might contribute to FT damage during infection.
Assuntos
Tubas Uterinas/metabolismo , Gonorreia/imunologia , Metaloproteinase 8 da Matriz/metabolismo , Neisseria gonorrhoeae/patogenicidade , Adulto , Tubas Uterinas/citologia , Tubas Uterinas/microbiologia , Tubas Uterinas/patologia , Feminino , Humanos , Imuno-Histoquímica , Metaloproteinase 3 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Técnicas de Cultura de Órgãos , RNA Mensageiro/análise , Inibidor Tecidual de Metaloproteinase-1/metabolismoRESUMO
á : Matrix metalloproteinases can modulate the inflammatory response through processing of cyto- and chemokines. Among them, MMP-14 is a non-dispensable collagenase responsible for the activation of other enzymes, triggering a proteolytic cascade. To identify the role of MMP-14 during the pro-inflammatory response, wildtype and Mmp14 -/- mice were challenged with lipopolysaccharide. MMP-14 levels decreased after endotoxemia. Mutant animals showed 100% mortality, compared to 50% in wildtype mice. The increased mortality was related to a more severe lung injury, an impaired lung MMP-2 activation, and increased levels of the alarmin S100A9. There were no differences in the expression of other mediators including Il6, Cxcl2, Tgfb, Il10, or S100a8. A similar result was observed in lung explants of both genotypes cultured in presence of lipopolysaccharide. In this ex vivo model, exogenous activated MMP-2 ameliorated the observed increase in alarmins. Samples from septic patients showed a decrease in serum MMP-14 and activated MMP-2 compared to non-septic critically ill patients. These results demonstrate that the MMP-14-MMP-2 axis is downregulated during sepsis, leading to a proinflammatory response involving S100A9 and a more severe lung injury. This anti-inflammatory role of MMP-14 could have a therapeutic value in sepsis. KEY MESSAGES: ⢠MMP-14 levels decrease in lungs from endotoxemic mice and serum from septic patients. ⢠Mmp14 -/- mice show increased lung injury and mortality following endotoxemia. ⢠Absence of Mmp14 decreases activated MMP-2 and increases S100A9 levels in lung tissue. ⢠MMP-14 ameliorates inflammation by promoting S100A9 cleavage by activated MMP-2.
Assuntos
Endotoxemia/enzimologia , Endotoxemia/metabolismo , Metaloproteinase 14 da Matriz/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Endotoxemia/induzido quimicamente , Feminino , Genótipo , Humanos , Lipopolissacarídeos/toxicidade , Pulmão/efeitos dos fármacos , Pulmão/enzimologia , Pulmão/metabolismo , Masculino , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 14 da Matriz/genética , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 8 da Matriz/genética , Metaloproteinase 8 da Matriz/metabolismo , Camundongos , Camundongos Mutantes , Pessoa de Meia-Idade , Sepse/enzimologia , Sepse/metabolismoRESUMO
BACKGROUND AND OBJECTIVE: No previous study has directly compared the levels of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) between smokers and individuals with diabetes mellitus (DM) with periodontitis. Therefore, the aim of this study was to evaluate the gene expression of MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1 and TIMP-2 in tissues with chronic periodontitis (ChP) of smokers and individuals with type 2 DM. MATERIAL AND METHODS: Gingival biopsies were harvested from: non-smokers and non-diabetic individuals with ChP (n = 18) (ChP group); non-diabetic smokers (≥ 10 cigarettes per day for at least the past 5 years) with ChP (n = 18) (SChP group); non-smoking individuals with type 2 diabetes (glycated hemoglobin levels ≥ 7.5%) and ChP (n = 18) (DMChP group). The tissue levels of mRNA of MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1 and TIMP-2 were evaluated by quantitative real-time polymerase chain reaction. RESULTS: The MMP-8 expression was the lowest in the ChP group (p < 0.05). The DMChP group presented increased mRNA levels of MMP-2 and MMP-9, when compared to the SChP group (p < 0.05). MMP-1 expression and the MMP-1/TIMP-1, MMP-2/TIMP-1, MMP-8/TIMP-1, MMP-9/TIMP-1, MMP-1/TIMP-2 and MMP-2/TIMP-2 ratios were higher in the DMChP group than in the ChP and SChP groups (p < 0.05). The DMChP group presented lower mRNA levels of TIMP-1 than the ChP group (p < 0.05). The MMP-8/TIMP-2 ratio was the highest in the SChP group (p < 0.05). CONCLUSION: Uncontrolled type 2 DM upregulates the ratio of MMP/TIMPs in sites with ChP more than smoking, which may contribute to a greater extracellular matrix degradation and periodontal breakdown in DM-related periodontitis.
Assuntos
Periodontite Crônica/complicações , Diabetes Mellitus Tipo 2/complicações , Metaloproteinases da Matriz/metabolismo , Fumar/efeitos adversos , Adulto , Periodontite Crônica/enzimologia , Periodontite Crônica/metabolismo , Diabetes Mellitus Tipo 2/enzimologia , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Gengiva/enzimologia , Gengiva/metabolismo , Humanos , Masculino , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 8 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismoRESUMO
BACKGROUND: Matrix metalloproteinases (MMPs) are responsible for the breakdown of the extracellular matrix and play an important role in the inflammatory processes of pleural exudates. The imbalance between MMPs and their inhibitors (TIMPs) is present in various pathological processes. OBJECTIVE: To evaluate the profile of MMPs and TIMPs in pleural effusions of different etiologies correlated with inflammatory markers. METHODS: The patients with pleural effusion due to tuberculosis (TB), cancer (CA) or transudate were prospectively evaluated. Pleural fluid was submitted to cytological, biochemical, cytokines, MMP, and TIMP analysis. Statistical analysis was performed using ANOVA and Spearman's correlation, and p < 0.05 was considered significant. RESULTS: One hundred and fourteen patients were enrolled, 80 exudates (41 TB and 39 CA) and 34 transudates. The levels of MMP-8 and MMP-9 were higher in exudates compared to transudates. The level of MMP-8 was significantly higher in TB than in CA. TIMP-1 levels were higher in exudates. IL-6, VEGF, and TGF-ß1 showed differences between exudates and transudates. However, IL-6 level was higher in TB than in CA. We found a significant correlation between MMPs and TIMPs with inflammation markers. MMP-1 was correlated with LDH levels. MMP-8 was correlated with LDH, total cell count, neutrophils, and ADA as well as MMP-1 levels. MMP-9 was correlated with IL-6, TGF-ß1, and VEGF. TIMP-1 was correlated with MMP-9 and IL-6. CONCLUSIONS: MMPs and TIMPs are expressed in pleural fluid of different etiologies and correlate with inflammatory mediators. MMPs may be useful in determining the cause of fluid, but more studies are needed to determine the spectrum of diseases associated with the various isoforms of MMPS and TIMPs.