Serum TIMP-1 Research Articles

Clinicopathologic and Prognostic Significance of Metalloproteinase Tissue Inhibitor-2 Promoters in Tunisian Colorectal Cancer: A Case-Control Study.

Tissue inhibitors of metalloproteinases (TIMPs) appear to affect many aspects of cancer biology, playing a crucial role in cell signaling by regulating cell growth, apoptosis, invasion, metastasis, angiogenesis, and genomic instability. In the present study, we investigate whether TIMP-2 SNP, TIMP-2 mRNAs, and TIMP-2 protein is associated with susceptibility to colorectal cancer (CRC) in Tunisian population. Taqman and DNA sequencing techniques were used for genotyping, TIMP-2 expression of each genotype was analyzed using semiquantitative RT-PCR and TIMP-2 protein expression was analyzed using immunohistochemistry staining. Our results showed that significantly elevated CRC risk was found in individuals with CC genotype (odds ratio 1.959; 95% confidence interval, 1.055-3.637). Moreover TIMP-2 mRNA expression in the colorectal cell carcinomas was significantly higher compared with the normal colorectal tissue (0.487±0.015 vs. 0.210±0.013) (P<0.05). In addition, serum levels of TIMP-2 were significantly lower in CRC patients than in adenoma patients (P=0.01) and healthy controls (P=0.003). Serum levels of TIMP-2 correlated significantly with tumor stage and TNM stage and were the lowest in CRC patients with stage D,T4,(N1,N2,N3),M(+). In conclusion, our study demonstrate for the first time the distribution and the clinical significance of TIMP-2 promoter polymorphisms, mRNA, protein expression, and serum level in CRC Tunisian patients suggesting that the genotyping and serum level of TIMP-2 as potential markers for susceptibility to CRC will allow a precise and early identification of individuals at high risk and will aid the design of therapeutic modalities and evaluation of treatment outcome.

Evaluation of matrix metalloproteinase, myeloperoxidase, and oxidative damage in mesenteric ischemia-reperfusion injury.

In this study, we investigated the alterations of matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinases (TIMPs), acute inflammation, and oxidative damage in the circulatory system and the intestine in response to mesenteric ischemia/reperfusion (I/R). Twenty-one rats were divided randomly into the following three groups (n = 7 in each group): a sham group (CG), an ischemic group (IG), and an I/R group (I/RG). MMP-9, TIMP-1, and myeloperoxidase (MPO) were measured using the enzyme-linked immunosorbent assay method, and lipid peroxidation (quantified as thiobarbituric acid reactive substances (TBARS) content), ischemia-modified albumin, the prooxidant-antioxidant balance (PAB), and ferric-reducing antioxidant power (FRAP) were measured spectrophotometrically. The degree of intestinal injury was evaluated according to the Chiu scoring system. A significant difference between the mean serum TIMP-1 and MMP-9 levels and the alanine transaminase activity was found among the groups. Compared with the I/RG group a significant difference in the mean tissue MMP-9, MPO, and TBARS levels in addition to the PAB and FRAP was found between the CG and IG groups. The level of MMP-9 also demonstrated a strong, positive, and valid correlation with the TBA-RS levels. A significant morphological change was observed in both the IG and the I/RG groups. The degree of intestinal injury was more severe in the I/R group and was characterized by either villous denudation or villous loss. These results suggest that MMP-9, TIMP-1, MPO, and oxidative stress may be important in the intestinal injury development that is induced by acute mesenteric I/R in a rat model. MMP-9 overexpression may increase the extent of intestinal villous loss, particularly when MMP-9 is upregulated by the TBARS present in the intestinal injury.

Age-Related Changes in the System Metalloproteinases/Tissue Metalloproteinase Inhibitors and Proteoglycan Components in Mouse Organs.

Activity of MMP and content of TIMP and some proteoglycan components were measured in the liver, lungs, and spleen of BALB/c mice aging 2, 6, and 12 months. The increase in the content of proteoglycan components in mouse organs was associated with age-related changes in MMP activity and TIMP-1 and TIMP-2 levels. The ratio between MMP activity and content of TIMP-1 and TIMP-2 differed in the studied organs. The levels of TIMP-1 and TIMP-2 in mouse blood serum and their concentration in studied organs changed asynchronously with age. They are important regulators that determine MMP activity in the analyzed age periods in mice, which can be determined as periods of growth, development, and ageing.

ECG low QRS voltage and wide QRS complex predictive of centenarian 360-day mortality.

We examined the electrocardiographic (ECG) findings of centenarians and associated them with >360-day survival. Physical and functional assessment, resting electrocardiogram and laboratory tests were performed on 86 study participants 101.9 ± 1.2 years old (mean ± SD) (70 women, 16 men) and followed for at least 360 days. Centenarian ECGs were assessed for left ventricular hypertrophy (LVH) according to the Romhilt–Estes score, Sokolow–Lyon criteria and Cornell voltage criteria which were positive for 12.8, 6.98, and 10.5 % of participants, respectively. Fifty-two study participants (60 %) survived ≥360 days. Multivariate logistic regression analysis revealed a negative relationship between 360-day survival and the following: R II <0.45 mV adjusted for CRP (odds ratio (OR) = 0.108, 95 % confidence interval (CI) = 0.034–0.341, P < .001), R aVF < 0.35 mV adjusted for CRP (OR = 0.151, 95 % CI = 0.039–0.584, P < .006), Sokolow–Lyon voltage <1.45 mV adjusted for CRP (OR = 0.178, 95 % CI = 0.064–0.492, P = .001), QRS ≥90 ms adjusted for CRP (OR = 0.375, 95 % CI = 0.144–0.975, P = .044), and Romhilt–Estes score ≥5 points adjusted for sex and Barthel Index (OR = 0.459, 95 % CI = 0.212–0.993, P = .048) in single variable ECG models. QRS voltage correlated positively with systolic and pulse pressure, serum vitamin B12 level, sodium, calcium, phosphorous, TIMP-1, and eGFR. QRS voltage correlated negatively with BMI, WHR, serum leptin, IL-6, TNF-α, and PAI-1 levels. QRS complex duration correlated positively with CRP; QTc correlated positively with TNF-α. Results suggest that Romhilt–Estes LVH criteria scores ≥5 points, low ECG QRS voltages (Sokolow–Lyon voltage <1.45 mV), and QRS complexes ≥90 ms are predictive of centenarian 360-day mortality.

Role of matrix metalloproteinases in the pathogenesis of childhood gastroenteritis.

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been implicated in the pathogenesis of gastrointestinal diseases, such as rotavirus gastroenteritis (GE). Kinetics of these biomarkers were examined in paired serum samples collected from bacterial enteritis patients with Campylobacter (n = 2) and Salmonella (n = 4) and viral GE patients with rotavirus (n = 27), norovirus (n = 25), and adenovirus (n = 11). At the time of hospital admission, all viral GE patients demonstrated increased MMP-9 and decreased MMP-2 and TIMP-2 serum levels. In contrast to viral GE patients, serum MMP-9 levels were not elevated at the time of hospital admission but elevated at the time of discharge; serum MMP-2 and TIMP-2 levels were decreased both at the time of admission and discharge in bacterial enteritis patients. Interestingly, the kinetics of serum MMP-2, MMP-9, and TIMP-2 levels were similar among the viral GE patients but distinct from bacterial enteritis patients. Thus, the involvement of MMPs and TIMPs in the pathophysiology of gastrointestinal symptoms likely varies depending on the etiological agent. Further studies are required to verify whether the extent of the bacterial enteritis or age of the patients influences these serum biomarkers. J. Med. Virol. 88:1341-1346, 2016. © 2016 Wiley Periodicals, Inc.

Circulating levels of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases during Japanese encephalitis virus infection.

Matrix metalloproteinases (MMPs) are widely implicated in modulating blood brain barrier (BBB) integrity and affect the entry of peripheral immune cells into the central nervous system (CNS). The expression of MMPs is tightly regulated at the level of gene transcription, conversion of pro-enzyme to active MMPs and by the action of tissue inhibitors of metalloproteinases (TIMP). The crucial role of MMPs in inflammation indicates that perturbation of the MMP/TIMP balance decisively plays an important role in pathogenesis during viral encephalitis. The study was performed to evaluate the production of MMP-2, MMP-7, MMP-9, TIMP-1 and TIMP-3 in the sera of JEV i.e. GP 78668A (GP-78) infected BALB/c mouse model of encephalitis and gel zymography was performed for MMP-2 and MMP-9 activities. The estimation of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-3 in JEV-infected mouse serum was analyzed by ELISA along with brain histopathology and immunohistochemistry. Evan's blue dye exclusion test was done to check the BBB integrity. Gelatin gel zymography was performed for MMP-2 and MMP-9 activities. We noticed an upregulated expression of MMPs in the sera of virus infected groups compared to controls at different days post inoculation (dpi). Post hoc analysis between days also reveals significant increase (p<0.05) in virus infected groups with disease progression. In contrast, TIMPs expressions were significantly (p<0.005) down regulated in the virus infected group. We provide preliminary evidence for a pattern of TIMP response in JEV infection distinct from that seen in acute inflammatory CNS conditions in JE, shown in our previous findings. Increased MMP-2 and MMP-9 activities were also found in a virus infected group with disease progression and are consistent with our previous finding of MMP-2 and MMP-9 activities in the CNS which clearly demonstrate worsen role of these immune mediators in JEV infection. This study will help to identify new targets for the therapeutic treatment of inflammatory mediated CNS disorders in JEV infection and may lead to the development of potential pharmacological targets in future.

Association of thalassemia major and gingival inflammation: A pilot study

ObjectivesThis cross-sectional study aimed to investigate the relationship between thalassemia major (TM) and gingival inflammation through the salivary, serum, and gingival crevicular fluid (GCF) levels of matrix metalloproteinase (MMP)-8, MMP-9 and tissue inhibitor of MMP (TIMP)-1. MethodsBiofluid samples and full-mouth clinical periodontal recordings were obtained from 29 otherwise healthy patients with TM and 25 systemically healthy (SH) individuals. Biofluid samples were evaluated by immunofluorometric assay (IFMA) and enzyme-linked immunoassays (ELISAs). Data were tested statistically by Kolmogorov Simirnov, Mann–Whitney U tests, Spearman correlation analysis. ResultsAge, smoking status, bleeding on probing, plaque index were similar in the study groups, but probing depth, gender data exhibited significant differences (p=0.037 for both). Salivary MMP-8, MMP-9, TIMP-1 concentrations were significantly higher in the TM than SH group (p=0.014; p<0.001; p=0.042, respectively). Serum TIMP-1 concentrations were significantly higher; MMP-8/TIMP-1, MMP-9/TIMP-1 molar ratios were significantly lower in the TM than SH group (p<0.001; p=0.005; p=0.022, respectively). Very few GCF samples revealed biochemical data above the detection limits. Numerous correlations were found between clinical periodontal parameters and biochemical data. ConclusionsIt may be suggested that TM may exacerbate the local inflammatory response as manifested in salivary MMP-8, MMP-9, TIMP-1 levels.

Temporal analysis of blood–brain barrier disruption and cerebrospinal fluid matrix metalloproteinases in rhesus monkeys subjected to transient ischemic stroke

Blood–brain barrier (BBB) disruption plays an important role in pathophysiological progress of ischemic stroke. However, our knowledge of the dynamic change of BBB permeability and its mechanism remains limited. In the current study, we used a non-human primate (NHP) MCAO model and a serial CSF sampling method that allowed us to determine the dynamic change of BBB permeability by calculating the CSF/serum albumin ratio (AR). We showed that AR increased rapidly and significantly after ischemia, and the fold increase of AR is highly correlated with the infarction size during the subacute phase. Moreover, we determined the temporal change of MMP-1, MMP-2, MMP-3, MMP-9, MMP-10, MMP-13, TIMP-1, and TIMP-2 in CSF and serum. Each MMP and TIMP showed different change patterns when comparing their values in CSF and serum. Based on the longitudinal dataset, we showed that the fold increase of MMP-9 in serum and CSF are both correlated to infarction size. Among the measured MMPs and TIMPs, only MMP-2, MMP-13, and TIMP-2 in CSF correlated with AR to some extent. Our data suggest there is no single MMP or TIMP fully responsible for BBB breakdown, which is regulated by a much more complicated signal network and further investigations of the mechanisms are needed.

Endurance and Resistance Training Affect High Fat Diet-Induced Increase of Ceramides, Inflammasome Expression, and Systemic Inflammation in Mice.

The study aimed to investigate the effects of differentiated exercise regimes on high fat-induced metabolic and inflammatory pathways. Mice were fed a standard diet (ST) or a high fat diet (HFD) and subjected to regular endurance training (ET) or resistance training (RT). After 10 weeks body weight, glucose tolerance, fatty acids (FAs), circulating ceramides, cytokines, and immunological mediators were determined. The HFD induced a significant increase in body weight and a disturbed glucose tolerance (p < 0.05). An increase of plasma FA, ceramides, and inflammatory mediators in adipose tissue and serum was found (p < 0.05). Both endurance and resistance training decreased body weight (p < 0.05) and reduced serum ceramides (p < 0.005). While RT attenuated the increase of NLRP-3 (RT) expression in adipose tissue, ET was effective in reducing TNF-α and IL-18 expression. Furthermore, ET reduced levels of MIP-1γ, while RT decreased levels of IL-18, MIP-1γ, Timp-1, and CD40 in serum (p < 0.001), respectively. Although both exercise regimes improved glucose tolerance (p < 0.001), ET was more effective than RT. These results suggest that exercise improves HFD-induced complications possibly through a reduction of ceramides, the reduction of inflammasome activation in adipose tissues, and a systemic downregulation of inflammatory cytokines.

The prognostic role of tissue and serum MMP-1 and TIMP-1 expression in patients with non-small cell lung cancer

PurposeMatrix metalloproteinase (MMP) and tissue inhibitor of matrix metalloproteinase (TIMP) play an important role in tumor invasion and progression. The aim of this study was to evaluate the prognostic role of MMP-1 and TIMP-1 in non-small cell lung cancer (NSCLC). To find out a potential serum biomarker, tissue and serum levels were investigated together. Patients and methodsFor 85 surgically resected NSCLC patients who had pre-operative serum samplings, MMP-1 and TIMP-1 expression were investigated using immunohistochemistry in tumor tissue and ELISA in serum. Tumor cells and surrounding stromal cells were assessed separately. ResultsHigher expression of MMP-1 in tumor cells comparing to stromal cells was related to male gender (P=0.006), ever smoker (P=0.004), and pooly differentiated tumor (P=0.043). For TIMP-1, adenocarcinoma showed higher tumor cell expression, while squamous cell carcinoma showed higher stromal expression (P=0.007). Patients with high carcinoembryonic antigen (CEA) level, the presence of vascular invasion, recurrence or death showed higher serum MMP-1 level. There was no correlation between the tissue and serum levels of MMP-1 and TIMP-1. A tumor/stroma TIMP-1 intensity ratio ≥1 was strongly associated with early recurrence in multivariate analysis (hazard ratio=280.55, 95% confidence intervals; 11.12–7080.45; P=0.001). High serum MMP-1 (≥3,500pg/ml) showed a trend for short overall survival (P=0.080). When serum MMP-1 was combined with CEA level or presence of vascular invasion, its prognostic implication was statistically significant (P=0.045 and P=0.015, respectively). ConclusionThe tumor/stroma TIMP-1 intensity ratio in tissue is useful to predict tumor recurrence. Serum MMP-1 level showed a possibility as a prognostic biomarker.

Diagnostic value of matrix metalloproteinase 9 and tissue inhibitor of matrix metalloproteinases 1 in cholesteatoma.

Matrix metalloproteinase 9 (MMP-9), able to degrade type IV collagen, plays a key role in inflammatory cell migration as well as in the destructive behaviour of cholesteatoma. The aim of our study was to compare the expression of MMP-9 and TIMP-1 in cholesteatoma tissue and in the concentrations in serum and plasma concentrations. Twenty five adult patients suffering from cholesteatoma (a study group) were included in the study. A comparison group consisted of 25 adult patients admitted to hospital due to nasal septum deviation. MM-9 and TIMP-1 serum and plasma concentrations as well as proteins' expressions in cholesteatoma tissues (study group) and normal retroauricular skin specimens (control group) were evaluated. MMP-9 and TIMP-1 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Cholesteatoma tissues and normal retroauricular skin specimens were evaluated immunohistochemically. In the study and a comparison groups, MMP-9 and TIMP-1 concentrations were similar with no significant difference within the groups. In cholesteatoma tissues, the expression of the investigated enzyme and its inhibitor was higher than in normal skin specimens, limited mostly to cholesteatoma perimatrix. Cholesteatoma may be limited to the middle ear or parts of the temporal bones. Our findings suggest better clinical usefulness of MMP-9 and TIMP-1 expression in cholesteatoma tissues than either serum or plasma levels of these proteins. It might suggest that the higher the expression of MMP-9 the stronger the inflammation -accompanied cholesteatoma.

Serum tissue inhibitor of matrix metalloproteinase-1 levels are associated with mortality in patients with malignant middle cerebral artery infarction.

BackgroundIn the last years, circulating matrix metalloproteinases (MMP)-9 levels have been associated with functional outcome in ischemic stroke patients. However the prognostic value of circulating levels of tissue inhibitor of matrix metalloproteinases (TIMP)-1 and MMP-10 in functional outcome of ischemic stroke patients has been scarcely studied. In addition, to our knowledge, serum MMP-9, MMP-10 and TIMP-1 levels in patients with malignant middle cerebral artery infarction (MMCAI) for mortality prediction have not been studied, and these were the objectives of this study.MethodsThis was a multicenter, observational and prospective study carried out in six Spanish Intensive Care Units. We included patients with severe MMCAI defined as Glasgow Coma Scale (GCS) lower than 9. We measured circulating levels of MMP-9, MMP-10, TIMP-1, in 50 patients with severe MMCAI at diagnosis and in 50 healthy subjects. Endpoint was 30-day mortality.ResultsPatients with severe MMCAI showed higher serum levels of MMP-9 (p = 0.001), MMP-10 (p < 0.001), and TIMP-1 (p = 0.02) than healthy subjects. Non-surviving MMCAI patients (n = 26) compared to survivor ones (n = 24) showed higher circulating levels of TIMP-1 (p < 0.001), MMP-10 (p = 0.02) and PAI-1(p = 0.02), and lower MMP-9 levels (p = 0.04). Multiple binomial logistic regression analysis showed that serum TIMP-1 levels > 239 ng/mL are associated with 30-day mortality (OR = 5.82; 95 % CI = 1.37-24.73; P = 0.02) controlling for GCS and age. The area under the curve for TIMP-1 as predictor of 30-day mortality was 0.81 (95 % CI = 0.67-0.91; P < 0.001). We found an association between circulating levels of TIMP-1 and MMP-10 (rho = 0.45; P = 0.001), plasminogen activator inhibitor (PAI)-1 (rho = 0.53; P < 0.001), and tumor necrosis factor (TNF)-alpha (rho = 0.70; P < 0.001).ConclusionsThe most relevant and new findings of our study, were that serum TIMP-1 levels in MMCAI patients were associated with mortality, and could be used as a prognostic biomarker of mortality in MMCAI patients.

Left ventricular diastolic dysfunction in patients with chronic obstructive pulmonary disease (COPD), prevalence and association with disease severity: Using tissue Doppler study

BackgroundChronic obstructive pulmonary disease (COPD) is a common preventable and treatable disease characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. It has some significant extra pulmonary effects that may contribute to its severity in individual patient. Among COPD patients, cardiovascular diseases (CVD) are responsible for approximately 50% of all hospitalizations and 20% of all deaths. Left ventricular diastolic dysfunction (LVDD) is a frequent condition in COPD patients. Inflammation is considered to be one of the systemic manifestations of COPD and provides an alternative hypothesis to explain the relationship between airflow limitation and cardiovascular risk. The present study aimed to assess the prevalence of LV diastolic dysfunction in COPD patients and its relation to the disease severity and presence of inflammatory markers. Patient and methodsForty nine (49) COPD patients were included in this study. All patients were subjected to full medical history, physical examination, chest roentgenogram, spirometry, laboratory blood testing for inflammatory mediators (C-reactive protein, matrix metalloproteinase-9 and tissue inhibitor metalloproteinase-1) and Echo Doppler study (conventional and tissue Doppler analysis). ResultsThe results showed that 36 COPD patients had LVDD (73.3%). There was a good correlation between LVDD parameters and COPD severity across GOLD stages and inflammatory markers. MMP-9 was statistically high in COPD patient with increasing severity with a p-value<0.0001. Also LVDD parameters were correlated with MMP-9 (p-value<0.00001). Other inflammatory markers were also correlated to the degree of airway obstruction (FEV1) and presence of LVDD. ConclusionThere is a high prevalence of LVDD in COPD patients which is associated with increased disease severity and associated with high levels of inflammatory markers (serum MMP-9 and TIMP-1). It is important to exclude decompensated heart failure during COPD exacerbation.

The imbalance between matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in acute pancreatitis.

The balanced activity of matrix metalloproteinases and their tissue inhibitors is an important, albeit still not completely understood, determinant of extracellular matrix homeostasis, a factor involved in the pathogenesis of acute pancreatitis (AP). The aim of this study was to compare serum concentrations of matrix metalloproteinase 9 (MMP-9) and its tissue inhibitor (TIMP-1) in patients with AP of various severity and to investigate their relationship with prognostic indicators of AP severity, e.g., polymorphonuclear leukocyte elastase (PMN-E). The study included 37 patients with mild (n = 18) or severe AP (n = 19) and 15 healthy controls. Serum concentrations of MMP-9 and TIMP-1 were determined on admission (day 1) and on days 2, 3, 5 and 10. Throughout the study period, the serum MMP-9 concentration in patients with severe AP was significantly higher than those in individuals with mild AP and in healthy controls. In turn, the serum MMP-9 concentrations in persons with mild AP did not differ significantly from those of the controls. The serum TIMP-1 concentrations in both groups were significantly higher than in the controls. Beginning from the 2(nd) day of hospital stay, the serum TIMP-1 concentration in patients with severe AP was significantly higher than in individuals with mild AP. There were significant correlations between: MMP-9 and PMN-E, TIMP-1 and PMN-E, and MMP-9 and TIMP-1. A disturbed balance between MMP-9 and TIMP-1 observed during the early stages of severe AP suggests that endogenous TIMP-1 is unable to prevent excessive activation and release of MMP-9. MMP-9 may represent a new marker of AP severity.

Gelatinase activities and TIMP-2 serum level in alcohol cirrhosis and chronic pancreatitis

There are some divergent data concerning the role of matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitor of MMP (TIMP)-2 in the pathogenesis of alcoholic cirrhosis (AC) and chronic pancreatitis (CP). Our objective was to evaluate the activity of MMP-2, MMP-9 and TIMP-2 serum levels in patients with AC and CP. Twenty-one patients with diagnosis of AC and twenty-two with CP admitted to the outpatient clinic for a control visit were enrolled. All results were compared with age and sex-matched control group (n=19). The sera obtained from venous blood were stored at -70°C for further analysis. Activity of MMP-2 and MMP-9 were evaluated with gelatin zymography, TIMP-2 serum level was analyzed with the usage of ELISA method. A significant decrease of serum MMP-2 activity was noted in sera of AC and CP patients in comparison with control. Activity of MMP-9 was elevated only in CP patients and TIMP-2 serum level was elevated only in AC patients. Decreased activity of MMP-2 in AC patients can contribute to cirrhosis development. The high level of MMP-9 in serum related to CP patients theoretically can exacerbate the inflammatory process within the pancreas.

Serum metalloproteinase-9 is related to COPD severity and symptoms - cross-sectional data from a population based cohort-study.

BackgroundChronic obstructive pulmonary disease, COPD, is an increasing cause of morbidity and mortality worldwide, and an imbalance between proteases and antiproteases has been implicated to play a role in COPD pathogenesis. Matrix metalloproteinases (MMP) are important proteases that along with their inhibitors, tissue inhibitors of metalloproteinases (TIMP), affect homeostasis of elastin and collagen, of importance for the structural integrity of human airways. Small observational studies indicate that these biomarkers are involved in the pathogenesis of COPD. The aim of this study was to investigate serum levels of MMP-9 and TIMP-1 in a large Swedish population-based cohort, and their association with disease severity and important clinical symptoms of COPD such as productive cough.MethodsSpirometry was performed and peripheral blood samples were collected in a populations-based cohort (median age 67 years) comprising subjects with COPD (n = 594) and without COPD (n = 948), in total 1542 individuals. Serum MMP-9 and TIMP-1 concentrations were measured with enzyme linked immunosorbant assay (ELISA) and related to lung function data and symptoms.ResultsMedian serum MMP-9 values were significantly higher in COPD compared with non-COPD 535 vs. 505 ng/ml (P = 0.017), without any significant differences in serum TIMP-1-levels or MMP-9/TIMP-1-ratio. In univariate analysis, productive cough and decreasing FEV1% predicted correlated significantly with increased MMP-9 among subjects with COPD (P = 0.004 and P = 0.001 respectively), and FEV1% predicted remained significantly associated to MMP-9 in a multivariate model adjusting for age, sex, pack years and productive cough (P = 0.033).ConclusionProductive cough and decreasing FEV1 were each associated with MMP-9 in COPD, and decreasing FEV1 remained significantly associated with MMP-9 also after adjustment for common confounders in this population-based COPD cohort. The increased serum MMP-9 concentrations in COPD indicate an enhanced proteolytic activity that is related to disease severity, and further longitudinal studies are important for the understanding of MMP-9 in relation to the disease process and the pathogenesis of different COPD phenotypes.

Serum MMP-8 and TIMP-1 in Critically Ill Patients With Acute Respiratory Failure

Serum MMP-8 and TIMP-1 in Critically Ill Patients With Acute Respiratory Failure

The Balance of Matrix Metalloproteinase-2 (Mmp-2) and Tissue Inhibitor of Matrix Metalloproteinase-2 (Timp-2) on Severe Endometriosis

The objective of this study is to examine the level balance of serum and peritoneal fluid MMP-2 and TIMP-2 in patients with severe endometriosis. The method of this study was a cross sectional study with twenty patients were diagnosed as severe endometriosis based on laparoscopy and laparotomy with five controls. Serum samples were taken before surgery, peritoneal fluid samples were taken during surgery, and MMP-2 and TIMP-2 examination was conducted in the end of the study by using ELISA method. The mean level of serum, peritoneal fluid MMP-2 and TIMP-2 were compared by using unpaired t-test. Based on this study, we found that MMP-2 level of serum and peritoneal fluid was significantly different in the case compared to the control, 5.848±3.016 vs. 1.600±0.063 ng/mL and 1.977±1.883 vs. 0.573±0.084 ng/mL respectively. When TIMP-2 level of serum and peritoneal fluid compared to the control, the significant difference was only found in serum (p < 0.05), 0.853±0.343 vs. 0.637±0.116 ng/mL and 1.339±2.141 vs. 0.105±0.028 ng/mL respectively. This study showed that there was an increase of MMP-2 level of serum and peritoneal fluid and low level of serum and peritoneal TIMP-2 in severe endometriosis. Serum and peritoneal fluid MMP-2 as well as TIMP-2 in serum had a significant relationship with the incidence of severe endometriosis. Meanwhile, TIMP-2 in peritoneal fluid had no significant relationship with the incidence of severe endometriosis.

Effects of natural eggshell membrane (NEM) on monosodium iodoacetate-induced arthritis in rats

Purpose: The aim of this study is to investigate anti-arthritis activity using natural eggshell membrane (NEM). Methods: NEM was administered at 52 mg/kg, 200 mg/kg, and 400 mg/kg to SD-Rat, where arthritis was induced by monosodium iodoacetate (MIA) at 3 mg. NO production in serum was measured using Griess reagent. Cytokines including IL-1β, and IL-6 were measured by Luminex and PGE2, MMP-2, MMP-9, TIMP-1, LTB4, and hs-CRP were measured by ELISA. The cartilage of patella volume was examined and 3-D high-resolution reconstructions of the cartilage of patella were obtained using a Micro-CT system. Results: Production of NO, IL-1β, IL-6, PGE2, MMP-2, MMP-9, TIMP-1, LTB4, and hs-CRP in serum was decreased, respectively, in comparison with control. The cartilage of patella volume increased significantly. In addition, the NEM group showed a decrease in the cartilage of patella, synovial membrane, and transformation of fibrous tissue. Conclusion: The results for NEM showed significant anti-arthritis activity. These results may be developed as a raw material for new health food to ease the symptoms mentioned above.

Elevated serum matrix metalloproteinase-2 and -9 and their correlations with severity of disease in patients with community-acquired pneumonia.

To determine the role of matrix metalloproteinases (MMPs) and their relationship with the clinical course of community-acquired pneumonia (CAP). Sixty-two consecutively hospitalized patients with CAP were enrolled and their pneumonia severity index (PSI), time to clinical stability (TCS), treatment response, and complications were recorded. The pre- and posttreatment serum concentrations of MMPs and their inhibitors were analyzed by ELISA. The activities of MMPs were evaluated by gelatin zymography. MMP-2 and -9 serum levels and their activities were higher in CAP patients than controls (P < 0.001 and P < 0.001, respectively). Low-risk patients had lower levels of MMP-2 and TIMP-1 than high-risk patients (P = 0.044, P = 0.001, respectively). Pretreatment serum TIMP-1 level was higher in patients with TCS of >3 days (P = 0.004) and was correlated with oxygenation and PSI scores. Posttreatment serum levels of MMP-9 and TIMP-1 were decreased after antibiotics (P = 0.000 1 and P = 0.0 17, respectively). Although MMP-2, MMP-9, and TIMP-1 correlate with many poor prognostic factors, more studies are required to prove their possible role in predicting the severity of CAP.