| 1. |
- Alm, Anna-Karin, et al.
(författare)
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Extrapancreatic trypsin-2 cleaves proteinase-activated receptor-2.
- 2000
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 275:1, s. 77-83
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Tidskriftsartikel (refereegranskat)abstract
- Proteinase-activated receptors (PARs) are activated by proteolytic removal of a short amino terminal peptide, thus exposing a new amino terminus that functions as a tethered ligand that activates the receptor. With the aim to identify and study potential activators of PAR-2 we have developed a new method to measure proteolytic cleavage of PARs. PAR-2 was tagged with the insulin C-peptide that upon receptor cleavage is released and quantified using an ELISA. The modified receptor, shown to be functional in mouse 3T3 cells, was expressed in an insect cell line and the ability of different proteinases to cleave PAR-2 was studied. Two different mast cell tryptases cleaved PAR-2 in a concentration dependent manner, but were much less potent than pancreatic trypsin and trypsin-2 isolated from a carcinoma cell line. Pancreatic trypsin and trypsin-2 were almost equally effective at cleaving PAR-2 suggesting that extrapancreatic trypsins are potential in vivo activators of PAR-2.
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| 2. |
- Hastbacka, Johanna, et al.
(författare)
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Matrix Metalloproteinases-8 and-9 and Tissue Inhibitor of Metalloproteinase-1 in Burn Patients. A Prospective Observational Study
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Matrix metalloproteinases (MMPs) -8 and -9 are released from neutrophils in acute inflammation and may contribute to permeability changes in burn injury. In retrospective studies on sepsis, levels of MMP-8, MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) differed from those of healthy controls, and TIMP-1 showed an association with outcome. Our objective was to investigate the relationship between these proteins and disease severity and outcome in burn patients. Methods In this prospective, observational, two-center study, we collected plasma samples from admission to day 21 post-burn, and burn blister fluid samples on admission. We compared MMP-8, -9, and TIMP-1 levels between TBSA<20% (N = 19) and TBSA>20% (N = 30) injured patients and healthy controls, and between 90-day survivors and non-survivors. MMP-8, -9, and TIMP-1 levels at 24-48 hours from injury, their maximal levels, and their time-adjusted means were compared between groups. Correlations with clinical parameters and the extent of burn were analyzed. MMP-8, -9, and TIMP-1 levels in burn blister fluids were also studied. Results Plasma MMP-8 and -9 were higher in patients than in healthy controls (P<0.001 and P = 0.016), but only MMP-8 differed between the TBSA<20% and TBSA>20% groups. MMP-8 and -9 were not associated with clinical severity or outcome measures. TIMP-1 differed significantly between patients and controls (P<0.001) and between TBSA<20% and TBSA>20% groups (P<0.002). TIMP-1 was associated with 90-day mortality and correlated with the extent of injury and clinical measures of disease severity. TIMP-1 may serve as a new biomarker in outcome prognostication of burn patients.
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| 3. |
- Hedenbjörk-Lager, Anders, et al.
(författare)
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Caries correlates strongly with salivary levels of Matrix Metalloproteinase-8
- 2015
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Ingår i: Caries Research. - : S. Karger. - 0008-6568 .- 1421-976X. ; 49:1, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- The caries process in dentin involves the degradation of both mineral and organic matrix. The demineralization has been demonstrated to be caused by bacterial acids. How-ever, the collagen degradation is considered to be initiated by endogenous proteolytic enzymes, mainly collagenolytic matrix metalloproteinases (MMPs). This paper aims to relate salivary MMP-8 (or salivary collagenase-2) and tissue inhibi-tor of MMP (TIMP-1) levels to manifest caries in a large num-ber of subjects. A random sample of 451 adults (aged 18-87 years) living in the south of Sweden was included in this study. Standard clinical examinations were performed, and stimulated saliva was collected and analyzed for concentra-tions of MMP-8, TIMP-1 and total protein, using an immuno-fluorometric assay, an enzyme-linked immunosorbent assay and the Bradford assay, respectively. Salivary numbers of mutans streptococci and lactobacilli were determined using a chair-side kit. Subjects with manifest caries lesions present-ed with elevated levels of MMP-8 (p < 0.001) as well as total protein, MMP-8/TIMP-1 ratio, bleeding on probing and plaque index (p = 0.05) compared with subjects without manifest caries. Multiple linear regression analysis with car-ies as the dependent variable revealed MMP-8 as the only significant explanatory variable (p < 0.001). TIMP-1 was not significant in any case. Using MMP-8 as the dependent vari-able revealed total protein concentration, caries lesions (p ≤ 0.001) and salivary secretion rate (p = 0.05) as explanatory variables. In conclusion, our data reveal that subjects with manifest caries lesions have elevated levels of salivary MMP-8 relative to subjects with no caries lesions.
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| 4. |
- Johansson, Anders, 1955-, et al.
(författare)
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Systemic Aggregatibacter Actinomycetemccomitans Leukotoxin-Neutralizing Antibodies in Periodontitis
- 2017
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Ingår i: Journal of Periodontology. - : Wiley. - 0022-3492 .- 1943-3670. ; 88:1, s. 122-129
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The leukotoxin expressed by Aggregatibacter actinomycetemcomitans is a powerful exotoxin, which can cause imbalance in the host response. Immunoreactivity to the leukotoxin is a marker for the presence of leukotoxic A. actinomycetemcomitan, a presence that may modify the disease pattern of the colonized individuals. The aim of the present study was to examine the presence of systemic immunoreactivity to A. actionmycetemcomitans leukotoxin in relation to clinical and inflammatory findings in individuals with or without periodontitis (n = 88).METHODS: The periodontal status was examined in a population of cases (n = 49) and controls (n = 39), and the cases received periodontal treatment. Systemic biomarkers associated with inflammation and infections, as well as the clinical parameters, were analyzed at baseline, three months after treatment and six months after.RESULTS: The presence of immunoreactivity against leukotoxin was associated with impaired remission of the disease after periodontal treatment. This immunoreactivity was also significantly associated with increased systemic levels of A. actinomycetemcomtans-specific immunoglobulins and increasing age.CONCLUSION: The presence and levels of systemic immunoreactivity against A. actinomycetemcomitans leukotoxin are associated with a decreased remission after otherwise successful periodontal treatment.
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| 5. |
- Kaasinen, Mirjami, et al.
(författare)
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Matrix Metalloproteinase 8 Expression in a Tumour Predicts a Favourable Prognosis in Pancreatic Ductal Adenocarcinoma
- 2022
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 23:6
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic ductal adenocarcinoma (PDAC) is a significant cause of cancer-related death globally, and, despite improvements in diagnostics and treatment, survival remains poor. Matrix metalloproteinases (MMPs) are enzymes involved in stroma remodelling in inflammation and cancer. MMP-8 plays a varied prognostic role in cancers of the gastrointestinal tract. We examined the prognostic value of MMP-8 immunoexpression in tumour tissue and the amount of MMP-8-positive polymorphonuclear cells (PMNs) in PDAC and their association with immune responses using C-reactive protein (CRP) as a marker of systemic inflammation. Tumour samples from 141 PDAC patients undergoing surgery in 2002–2011 at the Department of Surgery, Helsinki University Hospital were stained immunohistochemically, for which we evaluated MMP-8 expression in cancer cells and the amount of MMP-8-positive PMNs. We assessed survival using the Kaplan–Meier analysis while uni-and multivariable analyses relied on the Cox proportional hazards model. A negative MMP-8 stain and elevated CRP level predicted a poor prognosis (hazard ratio [HR] = 6.95; 95% confidence interval (CI) 2.69–17.93; p < 0.001) compared to a positive stain and low CRP level (<10 mg/L). The absence of PMNs together with an elevated CRP level also predicted an unfavourable outcome (HR = 3.17; 95% CI 1.60–6.30; p = 0.001). MMP-8 expression in the tumour served as an independent positive prognostic factor (HR = 0.33; 95% CI 0.16–0.68; p = 0.003). Tumour MMP-8 expression and a low CRP level may predict a favourable outcome in PDAC with similar results for MMP-8-positive PMNs and low CRP levels. Tumoural MMP-8 expression represents an independent positive prognostic factor in PDAC.
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| 6. |
- Lundmark, Anna, et al.
(författare)
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Mucin 4 and matrix metalloproteinase 7 as novel salivary biomarkers for periodontitis
- 2017
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Ingår i: Journal of Clinical Periodontology. - : John Wiley & Sons. - 0303-6979 .- 1600-051X. ; 44:3, s. 247-254
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Periodontitis is a chronic inflammatory disease, characterized by irreversible destruction of tooth-supporting tissue including alveolar bone. We recently reported mucin 4 ( MUC4) and matrix metalloproteinase 7 (MMP7) as highly associated with periodontitis in gingival tissue biopsies. The aim of this study was to further investigate the levels of MUC4 and MMP7 in saliva and gingival crevicular fluid (GCF) samples of patients with periodontitis. Materials and Methods: Saliva and GCF samples were collected from periodontitis patients and healthy controls. The levels of MUC4, MMP7, and total protein concentrations were analysed using ELISA or Bradford assay. Results: MUC4 levels were significantly lower in saliva and GCF from periodontitis patients relative to healthy controls. MMP7 levels were significantly higher in saliva and GCF from periodontitis patients. Multivariate analysis revealed that MUC4 was significantly associated with periodontitis after adjusting for age and smoking habits and, moreover, that the combination of MUC4 and MMP7 accurately discriminated periodontitis from healthy controls. Conclusions: MUC4 and MMP7 may be utilized as possible novel biomarkers for periodontitis.
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| 7. |
- Nilsson, Anna J. E., et al.
(författare)
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Enhanced Systemic Response of Matrix Metalloproteinases and Their Regulators in Campylobacter and Salmonella Patients
- 2018
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Ingår i: Diagnostics (Basel). - : MDPI AG. - 2075-4418. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- Campylobacters are major enteropathogens worldwide with a substantial financial burden. Matrix metalloproteinases (MMPs) are proteolytic metalloendopeptidases with ability to modify immune response and shown to be upregulated in patients with several tissue destructive diseases, including infections. We measured here serum concentrations of MMP-8 and MMP-9 together with their regulators myeloperoxidase (MPO), human neutrophil elastase (HNE), and tissue inhibitor of metalloproteinases (TIMP)-1 in 80 Campylobacter and 25 Salmonella patients as well as in 27 healthy controls. Paired serum samples were available for 73 and 23 patients, respectively. When the initial serum samples were compared to those from controls, both Campylobacter and Salmonella patients showed elevated concentrations of all biomarkers tested (p ≤ 0.037). In the follow-up samples, collected about 25 days afterwards, MMP-8 levels of Campylobacter patients had already turned to normal but all the other biomarkers still showed elevated, although from the initial levels significantly dropped, levels. For the follow-up samples of Salmonella patients, only MMP-9 and MPO levels were at a significantly higher level than in controls. It remains to be studied if the systematically enhanced neutrophil-derived proteolytic and oxidative stress, induced by Campylobacter infection as shown here and persisting for several weeks, is important for the development of late sequelae.
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| 8. |
- Odermarsky, Michal, et al.
(författare)
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HLA, infections and inflammation in early stages of atherosclerosis in children with type 1 diabetes
- 2018
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 1432-5233 .- 0940-5429. ; 55:1, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- Aims This prospective study focuses on risk factors for arterial damage in children with type 1 diabetes (T1D). Methods Eighty children and adolescents with T1D were investigated twice, approximately 2 years apart, for carotid artery intima-media thickness (cIMT) and compliance (CAC), flow-mediated dilatation (FMD) of the brachial artery, and plasma levels of matrix metalloproteinase (MMP)-8. All subjects were genotyped for HLA. The number of respiratory tract infections (RTI) during the past year was obtained by a questionnaire in 56 patients. Results cIMT progression, defined as percentage (%) change of cIMT from baseline, correlated inversely with the % changes of both CAC (p = 0.04, r = − 0.3; n = 62) and FMD (p = 0.03, r = − 0.3; n = 47). In multivariate analysis, RTI frequency correlated significantly with cIMT progression irrespective of age, diabetes duration, BMI, and HbA1c (p = 0.03, r = 0.3). When patients were divided in relation to RTI, the association of DQ2/8 with cIMT progression remained significant in patients with over three infections/year (p = 0.04, r = 0.3). During follow-up, the group of DQ2/8 patients with hsCRP > 1 mg/l showed significantly higher levels of plasma MMP-8 than the non-DQ2/8 group. Conclusions The diabetes-risk genotype DQ2/8 and systemic inflammation contribute to pro-atherosclerotic vascular changes in children and adolescents with T1D.
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| 9. |
- Odermarsky, M., et al.
(författare)
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Human Leucocyte Antigen, Infections and Systemic Inflammatory Biomarkers in Early Atherosclerosis in Children and Adolescents with Type 1 Diabetes
- 2015
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Ingår i: Cardiology in the Young. - 1467-1107. ; 25:Suppl. 1, s. 33-33
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Konferensbidrag (refereegranskat)abstract
- Background: This prospective study focuses on factors associated with arterial damage in children with type 1 diabetes (T1D). Materials and Methods: Eighty children and adolescents with T1D (mean age 15, range: 8-20 yrs; mean diabetes duration 7, range: 0.5 to 19 years) were investigated twice, approximately 2 years apart, for carotid artery intima-media thickness (cIMT) and compliance (CAC), flow-mediated dilatation (FMD) of the brachial artery, and plasma levels of matrix metalloproteinase (MMP)-8. HLA genotypes were determined in dried spots of peripheral blood by polymerase chain reaction followed by hybridization assay. The number of respiratory tract infections (RTI) during the past year was obtained by a questionnaire in 56 patients. Results: cIMT progression (% change of cIMT from baseline) correlated inversely with the % changes of both CAC (p = 0.04, r=−0.3, n=62) and FMD (p=0.03, r=−0.3, n=67). RTI frequency correlated significantly with cIMT progression irre- spective of age, diabetes duration, BMI, and HbA1c (p=0.03, r=0.3, in multivariate analysis). When patients were divided in relation to DQ2/8 genotype and RTI, the association of DQ2/8 with cIMT progression remained significant in patients with over three infections/year (p = 0.04, r = 0.3). During follow-up, the group of DQ2/8 patients with CRP > 1 mg/l showed significantly higher levels of plasma MMP-8 than the non-DQ2/8 group. Conclusions: Diabetes-risk genotype DQ2/8 and inflammation con- tribute to vascular changes in children and adolescents with T1D.
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| 10. |
- Pussinen, Pirkko J., et al.
(författare)
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The balance of serum matrix metalloproteinase-8 and its tissue inhibitor in acute coronary syndrome and its recurrence
- 2013
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 167:2, s. 362-368
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Tidskriftsartikel (refereegranskat)abstract
- Background: Matrix metalloproteinase-8 (MMP-8) is involved in the breakdown of the extracellular matrix increasing the vulnerability of atherosclerotic lesions. We analysed the diagnostic value of serum MMP-8 and tissue inhibitor of metalloproteinase-1 (TIMP-1) concentrations in acute coronary syndrome (ACS) and their prognostic value in ACS recurrence. Methods: The population comprised 343 patients with ACS [including 108 unstable angina pectoris and 235 acute myocardial infarctions (AMI)] and 326 healthy controls. Additionally, 157 (45.8%) patients were resampled during the recovery. The ACS patients were followed up for 6 years. Results: MMP-8, TIMP-1, and their molar ratio distinguished the cases from the controls; C-statistic of the multivariate model (95% CI, p-value) including the MMP-8/TIMP-1 ratio regarding its discriminating ability for AMI was 0.922 (0.893-0.950, p < 0.001). After the acute phase of ACS, median MMP-8 and TIMP-1 concentrations decreased (p < 0.001) by 34.5 and 28.7%, respectively, but ended up on a different level than those found in the controls. In the follow-up, acute phase and recovery period TIMP-1 concentrations associated with cardiovascular death with hazard ratios 4.31 (2.00-9.26, p < 0.001) and 4.69 (1.10-20.01, p = 0.037), respectively. Conclusions: The increase of serum MMP-8 and TIMP-1 concentrations may reflect plaque instability and tissue damage. TIMP-1 concentrations are associated with poor outcome in patients with ACS. The findings may have practical implications in both diagnostics and therapeutics. (c) 2011 Elsevier Ireland Ltd. All rights reserved.
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