Intrathecal synthesis of matrix metalloproteinase-9 in patients with multiple sclerosis: implication for pathogenesis

2002 ◽  
Vol 8 (3) ◽  
pp. 222-228 ◽  
Author(s):  
G M Liuzzi ◽  
M Trojano ◽  
M Fanelli ◽  
C Avolio ◽  
A Fasano ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Matrix Metalloproteinase ◽  
Neurological Diseases ◽  
Inverse Correlation ◽  
Serum Levels ◽  
Matrix Metalloproteinase 9 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Intrathecal Synthesis ◽  
Healthy Donors ◽  
Metalloproteinase 9

Matrix metalloproteinase-9 (MMP-9) was detected by zymography and enzyme-linked immunosorbent assay (ELISA) in matched serum and cerebrospinal fluid (CSF) samples from patients with neurological diseases. Patients with relapsing-remitting multiple sclerosis (RR-MS) had serum and CSF MMP-9 levels comparable to those from patients with inflammatory neurological diseases (INDs), but higher than patients with non-inflammatory neurological diseases (NINDs) and healthy donors (HDs). MMP-9 increased in active RR-MS in comparison with inactive RR-MS implying that MMP-9 in MS is related with clinical disease activity. A correlation between the CSF/serum albumin (QAlb) and CSF/serum MMP-9 (QMMP-9) was observed in IND and NIND but not in RR-MS patients, indicating that CSF MMP-9 levels in NIND and IND patients could be influenced by serum MMP-9 and blood-brain barrier (BBB) permeability properties. MS patients had higher values of QMMP-9:QAlb (MMP-9 index) than IND and NIND patients suggesting that in MS the increase in CSF MMP-9 could be due to intrathecal synthesis of MMP-9. A significant inverse correlation was found between MMP-9 and its endogenous inhibitor TIMP-1 in RR-MS indicating that in MS patients both the increase in MMP-9 and the decrease in TIMP-1 serum levels could contribute to BBB disruption and T-lymphocyte entry into the CNS.

Cerebrospinal fluid and serum levels and intrathecal production of active matrix metalloproteinase-9 (MMP-9) as markers of disease activity in patients with multiple sclerosis

2006 ◽  
Vol 12 (3) ◽  
pp. 294-301 ◽  
Author(s):  
E Fainardi ◽  
M Castellazzi ◽  
T Bellini ◽  
M C Manfrinato ◽  
E Baldi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Matrix Metalloproteinase ◽  
Disease Activity ◽  
Neurological Disorders ◽  
Serum Levels ◽  
Matrix Metalloproteinase 9 ◽  
Active Matrix ◽  
Magnetic Resonance Imaging Mri ◽  
Metalloproteinase 9

In this study, we employed a sensitive activity assay system to measure cerebrospinal fluid (CSF) and serum levels of active matrix metalloproteinase-9 (MMP-9) in 37 relapsing-remitting (RR), 15 secondary progressive (SP) and nine primary progressive (PP) multiple sclerosis (MS) patients, grouped according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. We also studied, as neurological controls, 48 patients with other inflammatory neurological disorders (OIND) and 48 with non-inflammatory neurological disorders (NIND). To assess active MMP-9/TIMP-1 circuit, CSF and serum levels of MMP-9 tissue inhibitor TIMP-1 were quantified by ELISA in the same patient population. CSF mean levels of active MMP-9, CSF active MMP-9/TIMP-1 ratios and intrathecal active MMP-9 synthesis, as indicated by specific index, were more elevated in MS than in NIND ( P <0.05, <0.02 and <0.02, respectively), serum active MMP-9/TIMP-1 ratio was higher in MS ( P<0.01) and OIND ( P<0.02) than in NIND, and serum TIMP-1 concentrations were lower in MS than in NIND ( P<0.05). More importantly, serum active MMP-9 mean levels, serum active MMP-9/TIMP-1 ratio and intrathecal production of active MMP-9 were increased in MS patients with clinical ( P<0.001, <0.001 and <0.05, respectively) and MRI ( P<0.001, <0.001 and <0.02, respectively) disease activity, whereas CSF mean concentrations of active MMP-9 and CSF active MMP-9/TIMP-1 ratio were enhanced only in MS patients with MRI evidence of disease activity ( P<0.02 and <0.01, respectively). Altogether, these findings suggest that a shift in MMP-9/TIMP-1 balance towards proteolytic activity of MMP-9 could be relevant in MS immune dysregulation. In addition, our results indicate that CSF and serum levels of active MMP-9 may represent a potential surrogate biomarker for monitoring MS disease activity. In particular, serum active MMP-9/TIMP-1 ratio seems to be a very appropriate indicator of ongoing MS inflammation, since it is easily measurable.

scholarly journals PECULIARITIES OF BRAIN-DERIVED NEUROTROPHIC FACTOR AND MATRIX METALLOPROTEINASE-9 EXPRESSION DYNAMICS IN PATIENTS WITH PARANOID SCHIZOPHRENIA DEPENDING ON THE DURATION OF THE DISEASE

2021 ◽  
Vol 74 (11) ◽  
pp. 2728-2732
Author(s):  
Ivan R. Romash ◽  
Mykhailo I. Vynnyk
Keyword(s):  
Matrix Metalloproteinase ◽  
Blood Serum ◽  
Neurotrophic Factor ◽  
Paranoid Schizophrenia ◽  
Serum Levels ◽  
Brain Derived Neurotrophic Factor ◽  
Matrix Metalloproteinase 9 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Group I ◽  
Metalloproteinase 9

The aim: To study the expression of brain-derived neurotrophic factor (BDNF) and matrix metalloproteinase-9 (MMP-9) in the blood serum of patients with paranoid schizophrenia and to trace the features of their dynamics depending on the duration of the disease and analyse the correlation between BDNF, MMP-9 serum levels and symptoms severity by using the Positive and Negative Syndrome Scale (PANSS). Materials and methods: The study included 120 patients, namely 20 patients with paranoid schizophrenia diagnosed less than 3 years ago (Сomparison Group) and 100 patients with a diagnosis of paranoid schizophrenia (Study Group): 20 of them have been suffering from this disease from 3 to 5 years (Subgroup I); 10 patients – from 5 to 10 years (Subgroup II); 10 patients – from 10 to 15 years (Subgroup III); 10 patients – from 15 to 20 years (Subgroup IV); 10 patients – from 25 years and more (Subgroup V). The groups did not differ with respect to age or gender. The content of BDNF and MMP-9 in blood serum was determined by enzyme-linked immunosorbent assay. Results: BDNF concentration averaged 28.327 ± 5.32 pg/ml in the patients of Group I; 25.40 ± 2.31 pg/ml in Group II; 24.32 ± 3.1 pg/ml in Group III; 23.8 ± 1.32 pg/ml in Group IV; 21.39 ± 0.97 pg/ml in Group V; 9.36 ± 4.38 pg/ml in Group VI. The expression of MMP-9 in the experimental groups constituted: 942.84 ± 87.80 pg/ml, 1042.84 ± 87.80 pg/ml, 1142.53 ± 77.20 pg/ml, 1752.84 ± 77.80 pg/ml, 1542.84 ± 37.70 pg/ml, 2042.74 ± 47.80 pg/ml, respectively. Decreased BDNF negatively correlated with MMP-9 expression (r=0.46; p<0.05). Conclusions: The development of paranoid schizophrenia was manifested by an imbalance in BDNF level and MMP-9 expression which could affect neurogenesis, synapticplasticity, ability to learn and remember, therefore, they could be considered as diagnostic markers of the pathology. With the increase in the duration of the studied pathology, BDNF parameters decreased and MMP-9 expression increased. A negative correlation between them was noted.

TIMP-1 resistant matrix metalloproteinase-9 is the predominant serum active isoform associated with MRI activity in patients with multiple sclerosis

2015 ◽  
Vol 21 (9) ◽  
pp. 1121-1130 ◽  
Author(s):  
Alessandro Trentini ◽  
Maria C Manfrinato ◽  
Massimiliano Castellazzi ◽  
Carmine Tamborino ◽  
Gloria Roversi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Matrix Metalloproteinase ◽  
Disease Activity ◽  
Serum Levels ◽  
Matrix Metalloproteinase 9 ◽  
Relapsing Remitting ◽  
Magnetic Resonance Imaging Mri ◽  
Specific Tissue ◽  
Metalloproteinase 9 ◽  
Ms Pathogenesis

Background: The activity of matrix metalloproteinase-9 (MMP-9) depends on two isoforms, an 82 kDa active MMP-9 modulated by its specific tissue inhibitor (TIMP-1), and a 65 kDa TIMP-1 resistant active MMP-9. The relevance of these two enzymatic isoforms in multiple sclerosis (MS) is still unknown. Objective: To investigate the contribution of the TIMP-1 modulated and resistant active MMP-9 isoforms to MS pathogenesis. Methods: We measured the serum levels of the 82 kDa and TIMP-1 resistant active MMP-9 isoforms by activity assay systems in 86 relapsing–remitting MS (RRMS) patients, categorized according to clinical and magnetic resonance imaging (MRI) evidence of disease activity, and in 70 inflammatory (OIND) and 69 non-inflammatory (NIND) controls. Results: Serum levels of TIMP-1 resistant MMP-9 were more elevated in MS patients than in OIND and NIND ( p < 0.05, p < 0.02, respectively). Conversely, 82 kDa active MMP-9 was higher in NIND than in the OIND and MS patients ( p < 0.01 and p < 0.00001, respectively). MRI-active patients had higher levels of TIMP-1 resistant MMP-9 and 82 kDa active MMP-9, than did those with MRI inactive MS ( p < 0.01 and p < 0.05, respectively). Conclusion: Our findings suggested that the TIMP-1 resistant MMP-9 seem to be the predominantly active isoform contributing to MS disease activity.

Matrix metalloproteinase-9 and matrix metalloproteinase-2 as biomarkers of various courses in multiple sclerosis

2009 ◽  
Vol 15 (3) ◽  
pp. 316-322 ◽  
Author(s):  
Y Benešová ◽  
A Vašků ◽  
H Novotná ◽  
J Litzman ◽  
P Štourač ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Matrix Metalloproteinase ◽  
Clinical Status ◽  
Serum Levels ◽  
Matrix Metalloproteinase 9 ◽  
Matrix Metalloproteinase 2 ◽  
Significant Elevation ◽  
Blood Brain Barrier Disruption ◽  
Mcdonald Criteria ◽  
Metalloproteinase 9

Background Matrix metalloproteinases are notable contributors to neuroinflammation and blood-brain barrier disruption in multiple sclerosis (MS). Objective The goal of this study was to determine the serum levels of matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-2 (MMP-2), and their tissue inhibitors (TIMP-1) and (TIMP-2), and to investigate their possible relations to type, disability, and severity of MS. Materials and methods Eighty-seven patients with definite MS according to the McDonald criteria and 50 healthy controls were enrolled in the study. Their clinical status was evaluated with the Expanded Disability Status Scale. Serum levels were analyzed by enzyme-linked immunoassay. Results A significant elevation in MMP-9 serum levels and in the MMP-9/TIMP-1 ratio was found in the whole MS group ( P < 0.001), in the relapsing–remitting MS (RRMS) ( P < 0.001), and secondary-progressive MS (SPMS) ( P < 0.001) groups when compared with the controls. A significant elevation in MMP-2 serum levels and in the MMP-2/TIMP-2 ratio was observed in the primary progressive ( P < 0.001) and the SPMS ( P < 0.002) groups when compared with the RRMS group, and this increase was also associated with the disability ( P < 0.001) and severity ( P < 0.05) of the disease. Conclusion We confirmed that metalloproteinases are useful biological markers in MS, providing information about the clinical type, disability, and severity of the disease.

How matrix metalloproteinase (MMP)-9 (rs3918242) polymorphism affects MMP-9 serum concentration and associates with autism spectrum disorders: A case-control study in Iranian population

2021 ◽  
pp. 1-7
Author(s):  
Javid Rezaei Lord ◽  
Farhad Mashayekhi ◽  
Zivar Salehi
Keyword(s):  
Serum Concentration ◽  
Matrix Metalloproteinase ◽  
Serum Levels ◽  
Autism Spectrum ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mmp9 Expression ◽  
Relationship Of ◽  
The Relationship ◽  
Metalloproteinase 9 ◽  
Control Study

Abstract The aim of this project was to evaluate the relationship of matrix metalloproteinase-9 (MMP-9) genetic variation and its serum concentration with autism spectrum disorder (ASD). One hundred ASD and 120 controls were enrolled in this study. Genomic DNA was extracted from blood and MMP-9 polymorphism was determined by polymerase chain reaction restriction fragment length polymorphism and serum levels were measured by enzyme-linked immunosorbent assay. The frequencies of CC, CT, and TT genotypes were 72%, 26%, and 2% in controls and 31%, 57%, and 12% in ASD, respectively. The frequencies of C and T alleles in ASD were 59.5% and 40.5%, and controls were 86% and 14%, respectively. There is a significant increase in serum MMP-9 levels in ASD as compared to controls. We have also shown that TT genotype is significantly associated with increase serum MMP-9 levels in patients (TT, CT, and CC serum levels were 91.77 ± 10.53, 70.66 ± 7.21, and 38.66 ± 5.52 and in controls were 55.55 ± 11.39, 42.66 ± 7.85, and 30.55 ± 6.34 ng/ml, respectively). It is concluded that there is a significant association between rs3918242 MMP-9 polymorphism and its serum concentration with autism. We also suggest that TT genotype is associated with increased MMP9 expression and may be a risk factor for ASD.

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