Periodontitis is characterized by periodontal tissue destruction. Since interleukin-17 (IL-17) has been reported to up-regulate IL-1β and tumor necrosis factor-alpha (TNF-α), it was hypothesized that ...it is increased in periodontitis and up-regulates these cytokines and tissue-destructive matrix metalloproteinases (MMP) in local migrant and resident cells. Immunocytochemistry disclosed elevated IL-1β, TNF-α, and IL-17 levels in periodontitis. These cytokines induced proMMP-1 and especially MMP-3 in gingival fibroblasts, whereas MMP-8 and MMP-9 were not induced. IL-17 was less potent as a direct MMP inducer than IL-1β and TNF-α, but it induced IL-1β and TNF-α production from macrophages, and IL-6 and IL-8 from gingival fibroblasts. In accordance with these findings, immunocytochemistry disclosed that MMP-1 and MMP-3 were increased in periodontitis. Gingival fibroblasts may play an important role in tissue destruction in periodontitis via cytokine-inducible MMP-1 and MMP-3 production, in which IL-17 plays a role as a key regulatory cytokine.
Background and Objective
Matrix metalloproteinase‐8 (MMP‐8) is involved in a wide range of pathologies including periodontitis and cardiovascular diseases (CVD). The association between periodontitis ...and CVD has been repeatedly recognized. The aim of the study was to analyze to what extent circulating active MMP‐8 (aMMP‐8) is associated with periodontal disease status and oral fluid aMMP‐8 levels in otherwise healthy subjects.
Material and Methods
In a cross‐sectional study, aMMP‐8 was measured in serum of 59 volunteers, comprising 19 periodontally healthy subjects, 20 patients with gingivitis as well as 20 with periodontitis. All study subjects were characterized regarding aMMP‐8 concentrations in different oral fluids as well as clinically and microbiologically with respect to periodontal disease. aMMP‐8 levels in gingival crevicular fluid were measured using the enzyme‐linked immunosorbent assay. Saliva enzyme levels as well as circulating aMMP‐8 were determined by a time‐resolved immunofluorometric assay. Both methods utilized the same monoclonal antibodies. Correlation and regression analyses were performed to study the potential association between serum aMMP‐8 and oral parameters.
Results
Oral aMMP‐8 levels were significantly higher in patients with periodontitis compared to periodontally healthy or gingivitis subjects. Highest serum aMMP‐8 concentration was also found in the periodontitis group. The serum levels correlated significantly with oral aMMP‐8 as well as with clinical parameters in a dose‐dependent manner. These results were confirmed in a multivariate regression analysis. After adjusting for potential confounders, saliva aMMP‐8 concentrations as well as periodontitis severity were significant predictors of serum aMMP‐8.
Conclusion
The associations between circulating aMMP‐8 and oral aMMP‐8 as well as periodontal findings in a dose‐dependent manner may contribute to linking periodontal disease with increased CVDsusceptibility.
Periodontitis is an infection characterized by the occurrence of supporting tissue destruction with an episodic nature. Disease progression is often determined by the loss of attachment level or ...alveolar bone, and sequential probing of periodontal attachment remains the most commonly utilized method to diagnose progressive destruction of the periodontium. The tolerance method has been the most extensive clinical method used in recent years to determine site-specific attachment level changes. There is abundant evidence that major tissue destruction in periodontal lesions results from the recruitment of immune cells. Considerable effort has been made to study the host cell and mediator profiles involved in the pathogenesis of chronic periodontitis, but the definition of active sites, where current periodontal breakdown occurs, and consecutive characterization of the mediators involved are still among the main concerns. In the present review, we summarize periodontopathic bacteria and host factors, including infiltrating cell populations, cytokines, and host matrix metalloproteinases, associated with under-going episodic attachment loss that could partly explain the mechanisms involved in destruction of the supporting tissues of the tooth.
Matrix metalloproteinases (MMPs) are a group of enzymes that in concert are responsible for the degradation of most extracellular matrix proteins during organogenesis, growth and normal tissue ...turnover. The expression and activity of MMPs in adult tissues is normally quite low, but increases significantly in various pathological conditions that may lead into unwanted tissue destruction, such as inflammatory diseases, tumour growth and metastasis. MMPs have a marked role also in tissue destructive oral diseases. The role of collagenases, especially MMP‐8, in periodontitis and peri‐implantitis is the best‐known example of the unwanted tissue destruction related to increased presence and activity of MMPs at the site of disease, but evidence has been brought forward to indicate that MMPs may be involved also in other oral diseases, such as dental caries and oral cancer. This brief review describes some of the history, the current status and the future aspects of the work mainly of our research groups looking at the presence and activity of various MMPs in different oral diseases, as well as some of the MMP‐related aspects that may facilitate the development of new means of diagnosis and treatment of oral diseases.
Background and Objective
The objective of this study was to evaluate the levels of MMP‐8, MMP‐9, TIMP‐1 and interleukin‐1beta (IL‐1β) in gingival crevicular fluid during the early and late stages of ...healing in gingival recession sites treated with coronally advanced flap plus platelet‐rich fibrin (CAF+PRF) compared with CAF plus connective tissue graft (CAF+CTG).
Material and Methods
Twenty‐four nonsmoking patients with Miller Class I or Class II localized gingival recession defects in bilateral sites received treatment with either CAF+PRF (PRF group) or CAF+CTG (CTG group). Gingival crevicular fluid samples were collected at baseline and at 10 d and 1 mo, 3 mo and 6 mo after surgery. The levels of MMP‐8, MMP‐9, TIMP‐1 and IL‐1β in gingival crevicular fluid were measured using a time‐resolved immunofluorometric assay and ELISAs.
Results
Gingival crevicular fluid levels of IL‐1β were significantly elevated in the CTG group at 10 d compared with baseline (p < 0.05). At 10 d after surgery, the levels of TIMP‐1 in gingival crevicular fluid showed a significant decrease in the CTG group compared with the PRF group (p < 0.05). The levels of IL‐1β and MMP‐8 in gingival crevicular fluid were significantly lower in the PRF group than in the CTG group at 10 d (p < 0.05). No significant differences were found in all clinical and biochemical parameters at 1, 3, and 6 mo between study groups (p > 0.05).
Conclusion
Root coverage with CAF+PRF has a significant effect on increasing gingival crevicular fluid TIMP‐1 levels and suppressing gingival crevicular fluid MMP‐8 and IL‐β levels at 10 d. Gingival crevicular fluid levels of MMP‐8, MMP‐9, TIMP‐1 and IL‐1β did not seem to be affected by the technique at later phases of wound healing.
Objective
MMP‐8 is a prominent collagenase in periodontal disease. This cross‐sectional study examined whether MMP‐8 levels in saliva and gingival crevicular fluid (GCF) are associated with ...periodontitis in a Swiss population.
Subjects and Methods
A total of 258 subjects (107 m, 151 f, mean age: 43.5 yr; range: 21–58 yr) acquired from the Swiss bone marrow donor registry participated in the study. Saliva and GCF samples were collected from subjects followed by a thorough dental and periodontal examination. MMP‐8 levels were determined with immunofluorometric assay. Associations of MMP‐8 levels with periodontal diagnosis, probing pocket depth (PPD) and bleeding on probing were statistically analysed with Pearson chi‐square test, Spearman's rho and logistic regression analysis.
Results
MMP‐8 in GCF correlated with MMP‐8 in saliva (p < .001). Periodontitis was more common (p < .001) among subjects with high levels of MMP‐8 in saliva and/or GCF compared with subjects with low levels of MMP‐8. Higher MMP‐8 levels in GCF and saliva were associated with any periodontal diagnosis (mild, moderate or severe), greater PPD, and bleeding on probing (p < .05). When age, gender, smoking, body mass index, number of medications and decayed, missing and filled teeth were adjusted for, all observed associations remained statistically significant. The area under curve of receiver‐operating characteristic was 0.67 for saliva and 0.71 for GCF.
Conclusion
Elevated MMP‐8 levels both in saliva and GCF are associated with periodontitis in a normal adult population.
Severe acute pancreatitis (SAP) has high morbidity and mortality but there are no widely accepted predictive biomarkers in clinical use. Matrix metalloproteinases (MMPs) are active in tissue ...destruction and inflammatory responses. We studied whether serum levels of activated MMP-8 (aMMP-8), MMP-9 and their regulators tissue inhibitor of matrix metalloproteinases (TIMP)-1, myeloperoxidase (MPO) and human neutrophil elastase (HNE) could predict the development of SAP.
The study comprised 214 AP patients (revised Atlanta classification: 142 mild, MAP; 54 moderately severe, MSAP; 18 SAP) referred to Helsinki University Hospital. A venous blood sample was taken within 72 h from the onset of symptoms. Serum levels of aMMP-8 were determined using immunofluorometric assay, and those of MMP-9, TIMP-1, MPO and HNE using enzyme-linked immunosorbent assay. AP groups were compared using Jonckheere-Terpstra test and predictive value for SAP was analyzed using receiver operating characteristics (ROC) analysis.
Serum aMMP-8 levels were higher in SAP (median 657 ng/ml, interquartile range 542–738 ng/ml) compared to MSAP (358 ng/ml, 175–564 ng/ml; p < 0.001) and MAP (231 ng/ml, 128–507 ng/ml; p < 0.001). Similar trend was seen with TIMP-1 and MPO. In ROC analysis aMMP-8, MPO and TIMP-1 emerged as potential markers for the development of SAP (areas under ROC curves 0.83, 0.71 and 0.69, respectively).
Serum aMMP-8 measured early in the course of AP (within 72 h of symptom onset) predicted the development of SAP.
Objective: The aim of the study was to compare four methods for gingival crevicular fluid (GCF) matrix metalloproteinase (MMP)‐8 detection.
Methods: Matrix metalloproteinase‐8 levels from 20 GCF ...samples from two periodontally healthy subjects, 18 samples from two patients with gingivitis and 45 samples from six patients with moderate to severe periodontitis, altogether 83 samples, were analysed using (1) a time‐resolved immunofluorometric assay (IFMA), (2) an MMP‐8 specific chair‐side dip‐stick test, (3) a dentoAnalyzer device and (4) the Amersham ELISA kit. Western immunoblot using same monoclonal anti‐MMP‐8 as in IFMA and dentoAnalyzer was used to identify molecular forms of MMP‐8 in GCFs.
Results: Correlation between IFMA and dentoAnalyzer results calculated with Spearman’s correlation coefficient was 0.95 (P = 0.01). The chair‐side dip‐stick test results were well in line with these assays. Periodontitis sites with unstable characteristics were differentiated with these methods. The Amersham ELISA results were not in line with the findings by other methods.
Conclusions: Immunofluorometric assay and dentoAnalyzer can detect MMP‐8 from GCF samples and these methods are comparable. Using Western immunoblot, it was confirmed that IFMA and dentoAnalyzer can detect activated 55 kDa MMP‐8 species especially in periodontitis‐affected GCF. dentoAnalyzer is among the first quantitative MMP‐8 chair‐side testing devices in periodontal and peri‐implant diagnostics and research.
Chronic biofilm infections are often accompanied by a chronic inflammatory response, leading to impaired healing and increased, irreversible damage to host tissues. Biofilm formation is a major ...virulence factor for Candida albicans and a challenge for treatment. Most current antifungals have proved ineffective in eradicating infections attributed to biofilms. The biofilm structure protects Candida species against antifungals and provides a way for them to evade host immune systems. This leads to a very distinct inflammatory response compared to that seen in planktonic infections. Previously, we showed the superior efficacy of dl-2-hydroxyisocaproic acid (HICA) against various bacteria and fungi. However, the immunomodulatory properties of HICA have not been studied. Our aim was to investigate the potential anti-inflammatory response to HICA in vivo. We hypothesized that HICA reduces the levels of immune mediators and attenuates the inflammatory response. In a murine model, a robust biofilm was formed for 5 days in a diffusion chamber implanted underneath mouse skin. The biofilm was treated for 12 h with HICA, while caspofungin and phosphate-buffered saline (PBS) were used as controls. The pathophysiology and immunoexpression in the tissues surrounding the chamber were determined by immunohistochemistry. Histopathological examination showed an attenuated inflammatory response together with reduced expression of matrix metalloproteinase 9 (MMP-9) and myeloperoxidase (MPO) compared to those of chambers containing caspofungin and PBS. Interestingly, the expression of developmental endothelial locus 1 (Del-1), an antagonist of neutrophil extravasation, increased after treatment with HICA. Considering its anti-inflammatory and antimicrobial activity, HICA may have enormous therapeutic potential in the treatment of chronic biofilm infections and inflammation, such as those seen with chronic wounds.
Summary
The amino acid derivative 2‐hydroxyisocaproic acid (HICA) is a nutritional additive used to increase muscle mass. Low levels can be detected in human plasma as a result of leucine metabolism. ...It has broad antibacterial activity but its efficacy against pathogenic fungi is not known. The aim was to test the efficacy of HICA against Candida and Aspergillus species. Efficacy of HICA against 19 clinical and reference isolates representing five Candida and three Aspergillus species with variable azole antifungal sensitivity profiles was tested using a microdilution method. The concentrations were 18, 36 and 72 mg ml−1. Growth was determined spectrophotometrically for Candida isolates and by visual inspection for Aspergillus isolates, viability was tested by culture and impact on morphology by microscopy. HICA of 72 mg ml−1 was fungicidal against all Candida and Aspergillus fumigatus and Aspergillus terreus isolates. Lower concentrations were fungistatic. Aspergillus flavus was not inhibited by HICA. HICA inhibited hyphal formation in susceptible Candida albicans and A. fumigatus isolates and affected cell wall integrity. In conclusion, HICA has broad antifungal activity against Candida and Aspergillus at concentrations relevant for topical therapy. As a fungicidal agent with broad‐spectrum bactericidal activity, it may be useful in the topical treatment of multispecies superficial infections.
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