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MMP-9 Levels (mmp-9 + level)
Selected AbstractsEvaluation of a magnetic resonance biomarker of osteoarthritis disease progression: doxycycline slows tibial cartilage loss in the Dunkin Hartley guinea pigINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 2 2009Jonathan Bowyer Summary The objective was to assess the effect of doxycycline treatment on a magnetic resonance imaging (MRI) biomarker of cartilage volume loss, and on matrix metalloproteinase (MMP) activity in a guinea pig osteoarthritis model. Guinea pigs (9 months old) were dosed with vehicle or doxycycline, 0.6, 3.0 mg/kg/day for 66 days. Fat-suppressed 3D gradient-echo MRI of the left knee was acquired pre- and post dosing. Change in medial tibial plateau (MTP) cartilage volume (MT.VC) was determined using image analysis. At termination, MTP cartilage was removed from knees and proteolytic MMP activity determined using a fluorescent peptide substrate assay. Vehicle-treated animals lost 20.5% (95% CI mean 25.6,15.1) MT.VC. The doxycycline (0.6 mg/kg/day) group lost 8.6% (P < 0.05, 95% CI 20.6 to ,5.3) whilst the 3.0 mg/kg/day group lost 10.0% (P < 0.05, 95% CI 13.9,6.0%). Endogenous levels of active MMPs were below limits of detection in all samples. However, doxycycline treatment ablated amino phenyl mercuric acid activated MMP-13 and MMP-8 levels, reduced MMP-9 levels by 65% and MMP-1 levels by 24%. Doxycycline treatment resulted in partial protection from MT.VC loss and was associated with complete reduction in MMP-13 and MMP-8, and partial reduction in MMP-9 activity. These data imply a role of MMPs in cartilage degeneration but incomplete protection suggests that additional doxycycline insensitive mechanisms are important in this model. The protective effect of doxycycline correlates with the clinical finding of lessened joint space narrowing, strengthens the utility of this animal model in identifying disease-modifying osteoarthritic drugs and supports the use of MRI biomarkers of cartilage loss. [source] Pro-inflammatory biomarkers during experimental gingivitis in patients with type 1 diabetes mellitus: a proof-of-concept studyJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 1 2010Giovanni E. Salvi Abstract Aim: To compare gingival crevicular fluid (GCF) biomarker levels and microbial distribution in plaque biofilm (SP) samples for subjects with type 1 diabetes (T1DM) versus healthy subjects without diabetes during experimental gingivitis (EG). Materials and Methods: A total of nine T1DM patients and nine healthy controls of age and gender similar to the T1DM patients were monitored for 35 days during EG. Hygiene practices were stopped for 3 weeks, and GCF, SP, plaque index (PI) and gingival index were determined. IL-1,, IL-8, MMP-8 and MMP-9 were quantified by enzyme-linked immunosorbent assay, and SP samples were assessed by DNA,DNA hybridization for a panel of 40 subgingival microbial species. Results: IL-1, levels in T1DM patients were elevated compared with healthy individuals, and showed differences between groups at 7,21 days while healthy patients showed IL-1, increases from baseline to 14,21 days (p<0.05). Differences were observed in MMP-9 levels between patients with and without T1DM at 7,14 days (p<0.05). Orange complex species and PI measurements displayed a superior correlation with biomarker levels when compared with other complexes or clinical measurements during EG. Conclusions: The mean GCF biomarker levels for IL-1, and MMP-8 were most significantly elevated in T1DM subjects compared with healthy individuals during EG, not resulting from differences in the mean PI or microbial composition. [source] Circulating matrix metalloproteinase 9 levels in relation to sampling methods, femoral and carotid atherosclerosisJOURNAL OF INTERNAL MEDICINE, Issue 6 2008F. J. Olson Abstract. Objectives., To examine whether circulating levels of matrix metalloproteinase 9 (MMP-9) were associated with ultrasound-assessed intima-media thickness (IMT) and echolucent plaques in the carotid and femoral arteries. To examine preanalytical sources of variability in MMP-9 concentrations related to sampling procedures. Subjects and design., Plasma and serum MMP-9 levels were compared with ultrasound assessed measures of femoral and carotid atherosclerosis, in a cross-sectional study of 61-year-old men (n = 473). Preanalytical sources of variability in MMP-9 levels were examined in 10 healthy subjects. Main outcome measures were circulating levels of MMP-9 in serum and plasma, IMT of the carotid and femoral arteries, and plaque status based on size and echolucency. Setting., Research unit at university hospital. Results., Plasma concentrations of total and active MMP-9 were associated with femoral artery IMT independently of traditional cardiovascular risk factors, and were higher in subjects with moderate to large femoral plaques. Plasma MMP-9 concentration was higher in men with echolucent femoral plaques (P = 0.006) compared with subjects without femoral plaques. No similar associations were found for carotid plaques. MMP-9 concentrations were higher in serum than in plasma, and higher when sampling was performed with Vacutainer than with syringe. MMP-9 levels in serum were more strongly associated with peripheral neutrophil count compared with MMP-9 levels in plasma. Conclusions., Plasma MMP-9 levels were associated with atherosclerosis in the femoral artery, and total MMP-9 concentration was higher in men with echolucent femoral plaques. The choice of sample material and sampling method affect the measurements of circulating MMP-9 levels. [source] Mobilization of CD133+CD34, cells in healthy individuals following whole-body acupuncture for spinal cord injuries,JOURNAL OF NEUROSCIENCE RESEARCH, Issue 8 2010Sonja Moldenhauer Abstract Acupuncture can alleviate symptoms of spinal cord injuries (SCI). The underlying mechanism, however, is unknown. We hypothesized that stem cells could be mobilized by acupuncture. Therefore, we enrolled 14 healthy study participants using acupuncture points for the treatment of SCI. The frequency of CD133 and CD34 cells in peripheral blood and the serum concentrations of matrix metalloproteinase (MMP)-9, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and interleukin-6 were determined before and after acupuncture (<1 hr, 24 hr, and 48 hr). CD133+34, cells were doubled 48 hr after acupuncture, with concomitant decreases in BDNF and MMP-9 levels. Interleukin-6 remained below detectable levels, eliminating a stress-induced cell release. Individuals acupunctured on control counterpoints showed no changes in CD133+ cells. Our results indicate that acupuncture for SCI can mobilize human CD133+34, cells. © 2009 Wiley-Liss, Inc. [source] Matrix metalloproteinase-7, -8, -9, -25, and -26 and CD43, -45, and -68 cell-markers in HIV-infected patients' saliva and gingival tissueJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 9 2006Liisa Mellanen Background:, Matrix metalloproteinases (MMPs) process the extracellular matrix and act in tissue remodelling in many physiological and pathological conditions. Certain MMPs can also exert protective anti-inflammatory properties. The levels and expression of MMPs and tissue inhibitors of MMPs (TIMPs) in saliva and gingival tissues of human immunodeficiency virus-seropositive (HIV+) patients are unclear. Methods:, Enzyme-linked immunosorbent assay methods and Western blots were used to study levels and molecular forms of MMP-7, -8, -9, -25, and -26 and TIMP-1 from salivary samples of HIV+ patients (n = 55) and healthy controls (n = 10). The expression of MMPs was also studied by immunohistochemical means in gingival tissue specimens (n = 11, HIV+ patients; n = 10, healthy controls). Results:, The HIV+ patients' MMP-8 levels in saliva were statistically significantly higher only in the acquired immunodeficiency syndrome (AIDS)-phase. MMP-9 levels in ASX- and AIDS-phases showed increased expression. TIMP-1 levels were significantly decreased in lymphadenopathy syndrome (LAS)- and AIDS-related complex (ARC)-phases, while MMP-8/TIMP-1 and MMP-9/TIMP-1 molar ratios were increased in all phases in comparison with controls. The molecular forms of MMP-7, -25, and -26 were different between patients and controls as assessed by Western blot. Immunohistochemical studies showed slightly enhanced MMP-7, -8, -9, -25, and -26 staining in HIV+ gingival tissue samples in comparison with controls. Conclusions:, This study confirmed and further demonstrated differences in salivary amounts and molecular forms of MMPs and TIMP-1 in HIV+ patients. The results may reflect alterations in host defence reactions associated with HIV infection. [source] Matrix metalloproteinase-9: a novel biomarker for monitoring disease activity in patients with chronic urticaria patients?ALLERGY, Issue 4 2009S. Altrichter Background:, Matrix metalloproteinase (MMP)-9, an enzyme that contributes to inflammatory responses and subsequent tissue remodelling, has recently been suggested to be a good biomarker for monitoring disease activity in patients with chronic urticaria (CU). Here, we assessed whether total MMP-9 and/or active MMP-9 plasma levels are increased and correlated to disease activity in patients with CU. Methods:, Total MMP-9 and active MMP-9 plasma levels were determined by ELISA in 70 CU patients and control subjects (patients with psoriasis and healthy controls). CU activity was measured using weekly and daily composite symptom scores (urticaria activity score) calculated from the number of wheals and the intensity of pruritus. Results:, Significantly increased levels of total and active MMP-9 were detected in patients with CU as compared to healthy controls. Interestingly, patients with psoriasis also had clearly elevated plasma levels of total and active MMP-9, indicating that MMP-9 plasma levels do not specifically reflect CU activity. Most notably, total and active MMP-9 levels were not correlated with disease activity in CU or psoriasis patients. Conclusion:, Plasma MMP-9 is not a good CU biomarker and should not be used for assessing the efficacy of treatment in CU patients or their spontaneous changes in disease activity. [source] German cockroach proteases regulate matrix metalloproteinase-9 in human bronchial epithelial cellsALLERGY, Issue 8 2006K. Page Background:, Matrix metalloproteinases (MMPs) digest extracellular matrix proteins and may play a role in the pathogenesis of bronchial asthma. MMP-9 levels are increased in the bronchoalveolar lavage fluid and sputum of asthmatics compared with that of controls. As exposure to cockroaches is an environmental risk factor for asthma, we sought to investigate the role of German cockroach fecal remnants (frass) on MMP-9 expression. Methods:, Human bronchial epithelial cells (16HBE14o-) and primary normal human bronchial epithelial cells were treated with cockroach frass in the absence or presence of tumor necrosis factor (TNF),. MMP-9 mRNA, protein levels and pro-MMP-9 activity were determined using real-time polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA) and zymogram assays. Pretreatment of frass with aprotinin abolished protease activity. PD98059, a chemical inhibitor of extracellular signal regulated kinase (ERK), and SLIGKV, an activator of protease-activated receptor (PAR)-2 were also used. AP-1DNA binding was determined by electrophoretic mobility shift assay (EMSA) and ERK phosphorylation by Western blot analysis. Results:, Cockroach frass augmented TNF, -mediated MMP-9 mRNA and protein expression by a mechanism dependent on active serine proteases within frass and not on endogenous endotoxin. Frass increased ERK phosphorylation, and chemical inhibition of ERK attenuated cockroaches' effects on MMP-9. Serine proteases are known to activate the PAR-2 receptor. We found that selective activation of PAR-2 using the peptide SLIGKV augmented TNF, -induced MMP-9 protein levels and increased ERK phosphorylation. Frass and SLIGKV each increased AP-1 translocation and DNA binding. Conclusions:, These data suggest that German cockroach frass contains active serine proteases which augment TNF, -induced MMP-9 expression by a mechanism involving PAR-2, ERK and AP-1. [source] Anti,apolipoprotein A-1 IgG predicts major cardiovascular events in patients with rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 9 2010Nicolas Vuilleumier Objective To determine whether anti,apolipoprotein A-1 (anti,Apo A-1) IgG are associated with major cardiovascular events in patients with rheumatoid arthritis (RA). Methods We determined anti,Apo A-1 IgG levels and the concentrations of cytokines, oxidized low-density lipoprotein (LDL), and matrix metalloproteinase 1 (MMP-1) MMP-2, MMP-3, and MMP-9 in sera from 133 patients with RA who did not have cardiovascular disease at baseline, all of whom were longitudinally followed up over a median period of 9 years. A major cardiovascular event was defined as a fatal or nonfatal stroke or acute coronary syndrome. The proinflammatory effects of anti,Apo A-1 IgG were assessed on human macrophages in vitro. Results During followup, the overall incidence of major cardiovascular events was 15% (20 of 133 patients). At baseline, anti,Apo A-1 IgG positivity was 17% and was associated with a higher incidence of major cardiovascular events (adjusted hazard ratio 4.2, 95% confidence interval 1.5,12.1). Patients who experienced a subsequent major cardiovascular event had higher circulating levels of anti,Apo A-1 IgG at baseline compared with those who did not have a major cardiovascular event. Receiver operating curve analysis showed that anti,Apo A-1 IgG was the strongest of all tested biomarkers for the prediction of a subsequent major cardiovascular event, with an area under the curve value of 0.73 (P = 0.0008). At the predefined and previously validated cutoff levels, the specificity and sensitivity of anti,Apo A-1 IgG to predict major cardiovascular events were 50% and 90%, respectively. Anti,Apo A-1 IgG positivity was associated with higher median circulating levels of interleukin-8 (IL-8), oxidized LDL, and MMP-9 and higher proMMP-9 activity as assessed by zymography. On human macrophages, anti,Apo A-1 IgG induced a significant dose-dependent increase in IL-8 and MMP-9 levels and proMMP-9 activity. Conclusion Anti,Apo A-1 IgG is an independent predictor of major cardiovascular events in RA, possibly by affecting vulnerability to atherosclerotic plaque. [source] Stromal-derived factor 1 and matrix metalloproteinase 9 levels in bone marrow and peripheral blood of patients mobilized by granulocyte colony-stimulating factor and chemotherapy.BRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2003Relationship with mobilizing capacity of haematopoietic progenitor cells Summary. The roles of the chemokine stromal-derived factor 1 (SDF-1) and the matrix metalloproteinase 9 (MMP-9) in haematopoietic progenitor cell (HPC) mobilization are still unclear, particularly when patients are mobilized by granulocyte colony-stimulating factor (G-CSF) plus chemotherapy. We determined bone marrow (BM) and peripheral blood (PB) plasma levels of SDF-1, together with CXC-chemokine receptor 4 (CXCR-4) expression on CD34+ cells, and interleukin 8 (IL-8) and MMP-9 in 55 patients mobilized for autologous PB transplantation compared with 10 normal BM and PB samples. Plasma samples were tested at steady state (SS-) and after mobilization by cyclophosphamide and G-CSF administration (M-). SDF-1, CXCR-4, IL-8 and MMP-9 levels were significantly lower in SS- and M-PB than in SS-BM. Differences in SDF-1 levels between SS-PB and SS-BM were also observed after mobilization. We showed for the first time a clear relationship between the levels of circulating HPC, both at steady state and after mobilization, and those of secreted MMP-9 but not of SDF-1 or IL-8. However, a negative correlation was observed between mobilizing capacity and CXCR-4 expression on CD34+ cells. These findings suggest that G-CSF-induced mobilization of HPC from BM involves MMP-9, without reversing the positive gradient of SDF-1 between BM and PB. [source] The role of matrix metalloproteinases -9 and -2 in development of neonatal chronic lung diseaseACTA PAEDIATRICA, Issue 6 2004DG Sweet Aim: Matrix metalloproteinases (MMPs) -9 and -2 degrade type-IV collagen, a major constituent of lung basement membrane, and may have a role in the pathogenesis of neonatal chronic lung disease (CLD). We determined factors influencing MMP levels in neonatal bronchoalveolar lavage (BAL) fluid to establish whether an imbalance between MMP and its inhibitor could be implicated in CLD. Methods: We measured MMP-9 and -2 and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels in 316 BAL fluid samples from 121 babies of gestational ages 23 to 42 wk over the first 14 d of life to determine effects of gestation and postnatal age. Median MMP-9, -2, TIMP-1 and MMP-9/TIMP-1 ratio in BAL were further studied in a subgroup of 85 babies >33 wk gestation to determine their ability to predict CLD and to establish effects of antenatal corticosteroid therapy (ANCS). Results: MMP-9, -2 and TIMP levels did not vary with postnatal age over the first week. Median MMP-9 levels and MMP-9/TIMP-1 ratio increased with decreasing gestation in preterm babies. The MMP-9/TIMP-1 ratio was higher in babies who developed CLD, implying a proteinase/antiproteinase imbalance, but this association disappeared when controlled for gestational age. ANCS had no effect on BAL fluid MMP or TIMP levels. Conclusion: MMPs may have a role in the development of lung injury and fibrosis, but estimating their levels in the first week of life does not help with prediction of CLD. [source] | ||||||||||