Induction of MMP-3 and MMP-9 expression during Helicobacter pylori infection via MAPK signaling pathways.

BACKGROUND AND AIMS: Helicobacter pylori (H. pylori)-induced gastric pathology involves remodeling of extracellular matrix mediated by aberrant activity of matrix metalloproteinases (MMPs). We have previously shown that in vitro H. pylori infection leads to MMP-3 and MMP-9 overexpression, associated with phosphorylation of bacterial oncoprotein CagA. We extended these findings in an in vivo model of H. pylori infection and further assessed the involvement of MAPK pathways in MMP expression. MATERIALS AND METHODS: C57BL/6 mice were infected with H. pylori strains HPARE, HPARE ΔCagA, and SS1, for 6 and 9 months. Transcriptional expression of Mmp-3 and Mmp-9 was evaluated via qPCR while respective protein levels in the gastric mucosa were determined immunohistochemically. Epithelial cell lines AGS and GES-1 were infected with H. pylori strain P12 in the presence of chemical inhibitors of JNK, ERK1/2, and p38 pathways, for 24 h. mRNA and protein expression of MMP-3 and MMP-9 were determined via qPCR and Western blot, respectively. RESULTS: We observed transcriptional activation of Mmp-3 and Mmp-9 as well as aberrant MMP-3 and MMP-9 protein expression in murine gastric tissue following H. pylori infection. CagA expression was associated with MMP upregulation, particularly during the early time points of infection. We found that inhibition of ERK1/2 resulted in reduced mRNA and protein expression of MMP-3 and MMP-9 during H. pylori infection, in both cell lines. Expressed protein levels of both MMPs were also found reduced in the presence of JNK pathway inhibitors in both cell lines. However, p38 inhibition resulted in a more complex effect, probably attributed to the accumulation of phospho-p38 and increased phospho-ERK1/2 activity due to crosstalk between MAPK pathways. CONCLUSIONS: H. pylori colonization leads to the upregulation of MMP-3 and MMP-9 in vivo, which primarily involves ERK1/2 and JNK pathways. Therefore, their inhibition may potentially offer a protective effect against gastric carcinogenesis and metastasis.

Evaluation of Gene Polymorphism and Gingival Crevicular Fluid Levels of Matrix Metalloproteinase-3 in a Group of Turkish Periodontitis Patients.

INTRODUCTION: Periodontitis is characterized by the destruction of tooth-supporting tissues. Matrix metalloproteinases (MMPs) play a significant part in the degradation of collagen structure. The gingival crevicular fluid (GCF) levels of MMPs increase with the progression of periodontal inflammation. Polymorphisms can be responsible for high expression of MMPs and can exacerbate the breakdown of collagen structure. This study aims to investigate the effect of MMP-3 -1171 5A/6A polymorphism and the GCF levels of MMP-3 in a group of Turkish periodontitis patients. MATERIALS AND METHODS: Non-smoking, stage II grade A periodontitis (S II-Gr A) (n = 68) and stage II grade B periodontitis (S II-Gr C) (n = 64) patients were recruited. Healthy individuals (H) (n = 72) without signs of gingivitis or periodontitis served as the control. Venous blood was collected from participants to obtain DNA, and the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to detect polymorphism. GCF samples were taken to assess MMP-3 levels using an enzyme-linked immunosorbent assay (ELISA). RESULTS: The MMP-3 -1179 5A/6A distribution showed no significant difference between the groups (p > 0.05). However, the MMP-3 GCF levels of the S II-Gr C group were higher than those of both the S II-Gr A and H groups (p < 0.05), and elevated MMP-3 levels were detected in S II-Gr A compared to H (p < 0.05). CONCLUSION: The MMP-3 GCF levels showed an association with periodontal tissue destruction, although single nucleotide polymorphism was not associated with the S II-Gr C and S II-Gr A groups in the Turkish population.

Cisatracurium attenuates LPS-induced modulation of MMP3 and junctional protein expression in human microvascular endothelial cells.

Acute respiratory distress syndrome (ARDS) is a life-threatening form of acute lung injury (ALI) associated with hypoxemic lung damage and inflammation. Matrix metalloproteinase protein-3 (MMP3 or Stromelysin-1) is known to promote vascular injury in ALI/ARDS. Cisatracurium, a nicotinic neuromuscular blocker, is used in ARDS patients to decrease mechanical ventilator dyssynchrony, increase oxygenation, and improve mortality. However, the magnitude and the underlying mechanisms of these potential benefits of cisatracurium remains unclear. We investigated the effect of cisatracurium on lipopolysaccharide-induced MMP3 expression in human microvascular endothelial cells. In our results, cisatracurium treatment significantly decreased LPS-induced MMP3 expression and increased expression of cell junction proteins such as vascular endothelial cadherin (VE-cadherin) and claudin-5.

Distinct effects of pharmacological inhibition of stromelysin1 on endothelial-to-mesenchymal transition and myofibroblast differentiation.

Endothelial-to-mesenchymal transition (EndMT) and fibroblast-to-myofibroblast (FibroMF) differentiation are frequently reported in organ fibrosis. Stromelysin1, a matrix metalloprotease-3 (MMP3) has been indicated in vascular pathologies and organ injuries that often lead to fibrosis. In the current study, we investigated the role of stromelysin1 in EndMT and FibroMF differentiation, which is currently unknown. In our results, whereas TGFß2 treatment of endothelial cells (ECs) induced EndMT associated with increased expression of stromelysin1 and mesenchymal markers such as α-smooth muscle actin (αSMA), N-cadherin, and activin linked kinase-5 (ALK5), inhibition of stromelysin1 blunted TGFß2-induced EndMT. In contrast, treatment of NIH-3T3 fibroblasts with TGFß1 promoted FibroMF differentiation accompanied by increased expression of αSMA, N-cadherin, and ALK5. Intriguingly, stromelysin1 inhibition in TGFß1-stimulated myofibroblasts further exacerbated fibroproliferation with increased FibroMF marker expression. Gene Expression Omnibus (GEO) data analysis indicated increased stromelysin1 expression associated with EndMT and decreased stromelysin1 expression in human pulmonary fibrosis fibroblasts. In conclusion, our study has identified that EndMT and FibroMF differentiation are reciprocally regulated by stromelysin1.

Pharmacological Inhibition of MMP3 as a Potential Therapeutic Option for COVID-19 Associated Acute Respiratory Distress Syndrome.

The high mortality of coronavirus disease 2019 (COVID-19) patients is due to their progression to cytokine-associated organ injuries, primarily the acute respiratory distress syndrome (ARDS). The uncertainties in the molecular mechanisms leading to the switch from the early virus infection to the advanced stage ARDS is a major gridlock in therapeutic development to reduce mortality. Previous studies in our laboratory have identified matrix metalloprotease-3 (MMP3) as an important mediator of bacterial lipopolysaccharide (LPS)-induced ARDS, particularly in the exudative phase. Our studies have also reported elevated plasma MMP3 activity levels in the ARDS patients and that inhibition of MMP3 can reduce the severity of LPS-induced ARDS in mice. Given these observations, targeting MMP3 could be a potential option to treat COVID-19 patients with ARDS, and measurement of MMP3 activity in the plasma may serve as a biomarker for the early detection of ARDS in COVID-19 patients.

Maxing xiongting mixture regulates factors relevant to lung reshaping and vascular remodeling of hypoxic pulmonary hypertension rats / 中国组织工程研究

BACKGROUND: Hypoxic pulmonary hypertension is a key link in the progression from chronic obstructive pulmonary disease to cor pulmonale. Its severity is closely related to disease development and prognosis. Current treatments cannot prevent or reverse disease progression. Maxing Xiongting Mixture has significant effect on hypoxic pulmonary hypertension with the syndrome of intermingled phlegm and blood stasis. OBJECTIVE: To study how the Maxing Xiongting Mixture regulates relevant factors of lung reshaping and vascular remodeling of hypoxic pulmonary hypertension rats with the syndrome of intermingled phlegm and blood stasis. METHODS: Seventy Sprague-Dawley rats, 5 weeks old, were randomly divided into normal group (n=10) and model group (n=60), where acute cor pulmonale model was prepared by injecting 50 mg/kg monocrotaline solution (1%) intraperitoneally, followed by forced smoking and swimming 6 days a week lasting for 4 weeks. Except for 10 rats in the normal group, there were 46 model rats in the model group. According to the normal distribution of body mass, 40 rats were selected and randomly divided into 4 groups: model group, high-dose Maxing Xiongting Mixture group (MH), low-dose Maxing Xiongting Mixture group (ML) and fasudil group, with 10 rats in each group. Rats in MH and ML groups were respectively given Maxing Xiongting Mixture at 20 g/(kg·d) and 5 g/(kg·d), respectively and those in the fasudil group were given fasudil at a dose of 10 mg/(kg·d). Other groups were given equal amount of saline. Administration was given intraperitoneally and intragastrically, once a day for 14 days in total. RT-PCR was used to test the expression of factors related to lung reshaping and vascular remodeling, including RhoA, stromelysin 1 and tumor necrosis factor-α mRNAs. An approval for the study was obtained from the Ethics Committee of Chengdu University of Traditional Chinese Medicine (approval No. 2017-03). RESULTS AND CONCLUSION: Compared with the model group, the expressions of RhoA, stromelysin 1, and tumor necrosis factor-α mRNAs were significantly lowered in the MH group (all P 0.05). To conclude, Maxing Xiongting Mixture, which is similar to fasudil, intervenes lung reshaping and vascular remodeling of hypoxic pulmonary hypertension rats with the syndrome of intermingled phlegm and blood stasis by inhibiting the expressions of RhoA, stromelysin 1, and tumor necrosis factor-α mRNAs.

Matrilysins and Stromelysins in Pathogenesis and Diagnostics of Cancers.

Matrix metalloproteinases (MMPs) are endopeptidases which are widely studied in terms of their role in the physiological and pathological processes in the organism. In this article, we consider usefulness of matrilysins and stromelysins in pathogenesis and diagnostic of the most common malignancies in the world, e.g., lung, breast, prostate, and colorectal cancers. In all of the mentioned cancers, matrilysins and stromelysins have a pivotal role in their development and also may have diagnostic utility. Influence to the cancerous process is connected with specific dependencies between these enzymes and components of the extracellular matrix (ECM), non-matrix components like cell surface components. All the information provided below allows to take a closer look at matrilysins and stromelysins and their functions in the cancer development.

Patients with acute respiratory distress syndrome exhibit increased stromelysin1 activity in the blood samples.

Enzyme activity analyses in the blood are expected to be reliable, non-invasive diagnostic as well as prognostic markers to reflect disease progression in acute lung injury (ALI). The objective of the current study was to evaluate the enzymatic activity of stromelysin1 (matrix metalloprotease-3) in the plasma/serum samples collected from ALI patients compared to the samples collected from healthy controls. Gene expression omnibus (GEO) database analysis indicated a correlation between increased stromelysin1 gene expression and the incidence of ALI in various animal models. Our analysis of patient plasma/serum samples from healthy controls and ALI patients revealed a significant, 3-fold increase in stromelysin1 activity in ALI plasma/serum compared to healthy subjects with no difference in stromelysin1 activity between the serum and plasma samples. Interestingly, no significant difference in stromelysin1 activity between non-smoking and smoking subjects was observed. These findings provide fundamental information on the potential reliability of stromelysin1 activity analysis, combined with other biomarkers in development, in blood samples for the early detection of ALI.

7­MEGA™ 500 regulates the expression of COX­2, MMP­3 and type 1 procollagen in UVB­irradiated human keratinocytes and dermal fibroblasts.

AlaskOmega® Omega 7 500, also known as Omega­7 fatty acid or 7­MEGA™, is a highly concentrated palmitoleic acid (C16:1). Little is known about how 7­MEGA regulates skin inflammation and wrinkle formation in cultured skin cells. The present study aimed to investigate the effects of 7­MEGA on the expression of cyclooxygenase­2 (COX­2), matrix metallopeptidase (MMP)­1/3 and type 1 procollagen, which are markers of skin inflammation and wrinkle formation, in ultraviolet B (UVB)­irradiated human dermal fibroblasts (HDFs) and keratinocytes (HaCaT). No toxicity was observed upon treatment of HDFs and HaCaT cells with 0.5­2.5 µl/ml 7­MEGA. The exposure of HaCaT cells to 10 mJ/cm2 UVB for 6 h resulted in increased protein and/or mRNA expression of COX­2 and MMP­3. Treatment of HaCaT cells with 2.5 µl/ml 7­MEGA suppressed the UVB­induced expression of COX­2 and MMP­3 in these cells. In addition, treatment with 2.5 µl/ml 7­MEGA attenuated the UVB­induced expression and phosphorylation levels of c­Fos and c­Jun, two components of the activator protein­1 (AP­1) transcription factor, in HaCaT cells. Exposure of HDFs to 60 mJ/cm2 UVB for 6 h significantly decreased the expression of type 1 procollagen protein, whereas treatment with 2.5 µl/ml 7­MEGA partially reversed the effects of UVB on the expression of type 1 procollagen protein. These results demonstrated for the first time that 7­MEGA regulated the expression of COX­2, MMP­3 and type 1 procollagen in UVB­irradiated skin cells. The present study suggested that 7­MEGA may serve as a novel agent against UVB­induced skin inflammation and damage.

Endothelial stromelysin1 regulation by the forkhead box-O transcription factors is crucial in the exudative phase of acute lung injury.

Enhanced vascular permeability is associated with inflammation and edema in alveoli during the exudative phase of acute respiratory distress syndrome (ARDS). Mechanisms leading to the endothelial contribution on the early exudative stage of ARDS are not precise. We hypothesized that modulation of endothelial stromelysin1 expression and activity by Akt1-forkhead box-O transcription factors 1/3a (FoxO1/3a) pathway could play a significant role in regulating pulmonary edema during the initial stages of acute lung injury (ALI). We utilized lipopolysaccharide (LPS)-induced mouse ALI model in vivo and endothelial barrier resistance measurements in vitro to determine the specific role of the endothelial Akt1-FoxO1/3a-stromelysin1 pathway in ALI. LPS treatment of human pulmonary endothelial cells resulted in increased stromelysin1 and reduced tight junction claudin5 involving FoxO1/3a, associated with decreased trans-endothelial barrier resistance as determined by electric cell-substrate impedance sensing technology. In vivo, LPS-induced lung edema was significantly higher in endothelial Akt1 knockdown (EC-Akt1-/-) compared to wild-type mice, which was reversed upon treatment with FoxO inhibitor (AS1842856), stromelysin1 inhibitor (UK356618) or with shRNA-mediated FoxO1/3a depletion in the mouse lungs. Overall, our study provides the hope that targeting FoxO and styromelysin1 could be beneficial in the treatment of ALI.

Narrowband ultraviolet B light treatment changes plasma concentrations of MMP-3, MMP-9 and TIMP-3 in psoriatic patients.

BACKGROUND: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are thought to be associated with the pathogenesis and spread of psoriatic disease. This study was designed to investigate the plasma levels of MMP-3, MMP-9 and TIMP-3 in plaque psoriasis patients prior to and following a course of ultraviolet B narrowband treatment with respect to disease advancement. METHODS: Plasma samples of 49 patients suffering from plaque psoriasis and 40 healthy volunteers were evaluated. Concentrations of MMP-3, MMP-9 and TIMP-3 were determined using enzyme-linked immunosorbent assay, while Psoriasis Area and Severity Index was used to define disease advancement. RESULTS: Plasma levels of MMP-3, MMP-9 and TIMP-3 were significantly elevated in psoriasis patients compared to healthy individuals. A course of ultraviolet B narrowband treatment resulted in a significant decline in the studied metalloproteinases. Furthermore, the concentration of selected tissue inhibitors was negatively correlated with baseline Psoriasis Area and Severity Index score. CONCLUSION: Our research highlights the meaningful role of MMP-3, MMP-9 and TIMP-3 in psoriasis pathogenesis and clearance of disease symptoms. Furthermore, plasma levels of the analyzed metalloproteinases seem to be a valuable psoriasis biomarker.

Association of matrix metalloproteinase 3 and γ-glutamyltransferase 1 gene polymorphisms with the cardio-ankle vascular index in young Russians.

Specific gene polymorphisms are known to be associated with a different arterial physiology in the younger generation. The present study found that young Russians with the matrix metalloproteinase 3 6A/6A and γ-glutamyltransferase 1AA genotypes have lower levels of the cardio-ankle vascular index - a recent measure of arterial stiffness. This observation may serve as an additional tool for cardiovascular disease prevention in the young population.

Helicobacter pylori CagA protein induces factors involved in the epithelial to mesenchymal transition (EMT) in infected gastric epithelial cells in an EPIYA- phosphorylation-dependent manner.

As a result of Helicobacter pylori adhesion to gastric epithelial cells, the bacterial effector cytotoxin-associated gene A (CagA) is translocated intracellularly, and after hierarchical tyrosine phosphorylation on multiple EPIYA motifs, de-regulates cellular polarity and contributes to induction of an elongation and scattering phenotype that resembles the epithelial to mesenchymal transition (EMT). Stromelysin-1/matrix metalloproteinase-3 (MMP-3) has been reported to induce a sequence of molecular alterations leading to stable EMT transition and carcinogenesis in epithelial cells. To identify the putative role of CagA protein in MMP-3 induction, we exploited an experimental H. pylori infection system in gastric epithelial cell lines. We utilized isogenic mutants expressing CagA protein with variable numbers of EPIYA and phosphorylation-deficient EPIFA motifs, as well as cagA knockout and translocation-deficient cagE knockout strains. Increased levels of MMP-3 transcriptional activation were demonstrated by quantitative real time-PCR for strains with more than two terminal EPIYA phosphorylation motifs in CagA. MMP-3 expression in total cell lysates and the corresponding culture supernatants was associated with CagA expression and translocation and was dependent on CagA phosphorylation. A CagA EPIYA phosphorylation-dependent increase in gelatinase and caseinolytic activity was also detected in culture supernatants by zymography. A significant increase in the transcriptional activity of the mesenchymal markers Vimentin, Snail and ZEB1 and the stem cell marker CD44 was observed in the case of CagA containing phosphorylation-functional EPIYA motifs. Our data suggest that CagA protein induces EMT through EPIYA phosphorylation-dependent up-regulation of MMP-3. Moreover, no significant increase in EMT and stem cell markers was observed following infection with H. pylori strains that cannot effectively translocate CagA protein.

Impact of 5A/6A polymorphism of matrix metalloproteinase-3 on recurrent atherosclerotic ischemic stroke in Chinese.

Little is known about the impact of the 5A/6A polymorphism of matrix metalloproteinase-3 (MMP-3) on recurrence of atherosclerotic ischemic stroke in Chinese. The aim of this study was to investigate the association of MMP-3 serum level and 5A/6A genetic polymorphism with the recurrence of atherosclerotic ischemic stroke in the Chinese Han population. We analyzed 106 large artery atherosclerosis (LAA) recurrent ischemic stroke patients and 545 LAA first onset ischemic stroke patients from January 2009 to June 2014. Serum MMP-3 concentrations were measured with an enzyme-linked immunosorbent assay. The genotypes of MMP-3 promoter polymorphism (-1171 5A/6A) were determined using polymerase chain reaction-restriction fragment length polymorphism. The frequencies of MMP-3 5A/6A+5A/5A (32.08% vs. 21.47%, p = 0.02) genotype and 5A (16.98% vs. 11.01%, p = 0.01) allele in the recurrent group was significantly higher than those in the first onset group. After adjustment for vascular risk factors, multivariate logistic regression analysis suggested that the MMP-3 5A/6A+5A/5A genotype was an independent risk factor for LAA recurrent ischemic stroke (odds ratio [OR], 1.74; 95% confidence interval [CI], 1.09-2.79, p = 0.021). No significant difference was observed for the MMP-3 serum concentrations between the recurrent group and the first onset group (22.23 ± 8.31 vs. 21.49 ± 7.89 ng/ul, t = 0.88, p = 0.38). The MMP-3 (-1171 5A/6A) polymorphism may contribute to LAA recurrent ischemic stroke susceptibility. Analysis of 5A/6A polymorphism in MMP-3 may identify patients at higher risk for LAA ischemic stroke recurrence, who may be selected for intensive preventive therapy.

RETRACTED: Proinflammatory cytokines induce stromelysin-1-mediated cell proliferation in dental pulp fibroblast-like cells.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of a member of the author team as it contains fabricated/falsified data. All of the authors except Nobuaki Ozeki and Taiki Hiyama have agreed to retract the article; N Ozeki left Aichi Gakuin University in March 2018 and does not respond to coauthor inquiries. T Hiyama left Aichi Gakuin University and could not be reached.

Changes of matrix metalloproteinase and cytokines and its clinical significance in children with juvenile idiopathic arthritis / 中华风湿病学杂志

Objective The purpose of the study was to investigate the changes and clinical significance of matrix metalloproteinase (MMP)-1,MMP-3,tissue inhibitor of metalloproteinase (TIMP),interleukin (IL)-1,tumor necrosis factor (TNF)-α and transforming growth factor(TGF)-β in juvenile idiopathic arthritis (JIA).Methods Thirty-two JIA subjects and 28 controls (traumatic arthritis patients) were included into this study.The MMP-1,MMP-3,TIMP,IL-1,TNF-α and TGF-β level in the serum and synovia were assessed by ELISA.The WBC count,the level of CRP,ESR,RF were also detected.Independent t-test and Pearson's analysis were adopted for data analysis.Results ① The level of MMP-1,MMP-3,IL-1 and TNF-α in the serum was (158±67) ng/ml,(212±89) ng/ml,(39±19) pg/ml,(26±10) pg/ml respectively,which was significantly higher than that of the control group (all P＜0.05) ; the ratio of MMP-3/TIMP-1 (0.86±0.32) was higher in the study group than that of the control group (P＜0.05),while the value of TIMP-1,TGF-β was (248±88),(17±9) ng/ml respectively,which was lower than that of the control group (P＜0.05).The value of seral MMP-3,MMP-3/TIMP-1 was positively correlated with that of WBC,CRP,ESR in the JIA group (all P＜0.05).② The value of MMP-1,MMP-3,IL-1 and TNF-α in the synovia was (216±78) ng/nl,(766±291)ng/ml,(56±21) pg/ml,(36±14) pg/ml respectively,which was higher than that of the control group (all P＜0.05); the ratio of MMP-3/TlMP-1 (2.68±0.89) was higher than that of the control group (P＜0.05),while the value of TIMP-1,TGF-β was (286±88) ng/ml,(12±4) ng/ml respectively,which was lower than that of the control group (all P＜0.05).③ The value of MMP-1,MMP-3,TIMP-1,IL-1 and TNF-α in the synovia was higher than that in the serum (all P＜0.05),while the value of TGF-β was lower than that in the serum (P＜0.05).Conclusion The value of MMP-1,MMP-3,IL-1 and TNF-α increases both in the serum and synovia,while the value of TIMP-1 decreases.The value of TGF-β decreases,which may have protective effect on JIA.The ratio of MMP-3/TIMP-1 in the serum is positively correlated to inflammation parameters,which may be used to judge the activity of illness in JIA.

Lack of an association between connexin-37, stromelysin-1, plasminogen activator-inhibitor type 1 and lymphotoxin-alpha genes and acute coronary syndrome in Czech Caucasians.

BACKGROUND: The majority of acute coronary syndrome (ACS) cases cannot be explained by the analysis of commonly recognized risk factors; thus, the analysis of possible genetic predispositions is of interest. The genes for connexin-37, stromelysin-1, plasminogen activator-inhibitor type 1 (PAI-1) and lymphotoxin-alpha are among many presently known candidate genes that are associated with risk factors for ACS. OBJECTIVE: To identify the potential impact of the functional variants of connexin-37, stromelysin-1, PAI-1 and lymphotoxin-alpha on ACS in a Caucasian Czech population. METHODS: A total of 1399 consecutive patients (1016 men and 383 women) with ACS from five coronary care units located in Prague (Czech Republic) were analyzed; a representative sample of 2559 healthy individuals (1191 men and 1368 women) were also genotyped and served as controls. RESULTS: The gene variants analyzed were not significantly associated with the prevalence of ACS or the classical risk factors of ACS development such as high plasma lipid levels, hypertension, diabetes, high body mass index or smoking. CONCLUSION: In a Caucasian Czech population sample, genetic variants of connexin-37, stromelysin-1, PAI-1 and lymphotoxin-alpha were not significantly associated with a predisposition toward ACS.

Morphological studies on osteoarthritis of the articular cartilage in C57 black mice and its relationship with etalloproteinase-3 and lnterleukln-1 in serum and synovial fluid / 中华风湿病学杂志

Objective To study the levels of Matrix Metalloproteinase-3 (MMP-3) and interleukin (IL-1) in the synovial fluid and plasma of C57 black mice with osteoarthritis (OA) and their relationships with the severity of pathological changes so as to investigate their effects and correlation with OA. Methods The C57 black mice with OA were enrolled for this study. Different levels of exercise were appicated based on their age. Knee joint pathological changes were examined for pathological severity of OA. ELISA sandwich method was used to measure the levels of MMP-3 and IL-1 in serum and synovial fluid. Correlation analysis was performed to demonstrate the relationship between the levels of MMP-3 and IL-1 in the serum and synovial fluid, and the pathological severity of OA. Results ①Morphological observations: C57 black mice were characterized by spontaneously developing OA and the incidence and the severity of osteoarthritis gradually increased with age and exercising burdens. ② The level of MMP-3 and IL-1 in the synovial fluid of exercising mice MMP-3 (84±6) ng/ml, IL-1 (48±3) ng/ml was higher than that in the aged ones [MMP-3 (84±6) ng/ml, IL-1 (71±5) ng/ml J, the difference was significant (P<0.01). The level of MMP-3 and IL-1 level in the serum had a linear correlation with that of the synovial fluid. At the same time, they also had linear correlation with the pathological severity of OA (All r>0.67, and all P<0.01). Conclusion The levels of MMP-3 and IL-1 in serum and synovial fluid can help to make early diagnosis of OA, especially elevated MMP-3 level.

Stromelysin-1 and Membrane type-MMP-1 Expressions in Human Chronic Periodontitis with Type 2 Diabetes Mellitus / 대한치주과학회지

PURPOSE: The purposes of this study were to compare and quantify the expression of Stromelysin-1 and MT-MMP-1 in the gingival tissues of patients with type 2 diabetes mellitus(DM) and healthy adults with chronic periodontitis. MATERIALS AND METHODS: Gingival tissue samples were obtained during periodontal surgery or tooth extraction. According to the patient's systemic condition & clinical criteria of gingiva, each gingival sample was devided into three groups. Group 1 (n=8) is clinically healthy gingiva without bleeding and no evidence of bone resorption or periodontal pockets, obtained from systemically healthy 8 patients. Group 2 (n=8) is inflammed gingiva from patients with chronic periodontitis. Group 3 (n=8) is inflammed gingiva from patients with chronic periodontitis associated with type 2 DM. Tissue samples were prepared and analyzed by Western blotting. The quantification of Stromelysin-1 and MT-MMP-1 were performed using a densitometer and statistically analyzed by one-way ANOVA followed by Tukey test. RESULTS: In the analysis of expression levels, Stromelysin-1 and MT-MMP-1 expressions were similar in group 1 and 2. Stromelysin-1 and MT-MMP-1 expressions was more increased in group 3 than group 1, 2. The difference between group 3 and group 1, 2 was statistically significant. Also, in the interrelationship of Stromelysin-1 and MT-MMP-1 expressions, expressions of Stromelysin-1 and MT-MMP-1 showed increasing tendency in chronic periodontitis associated with type 2 DM and it seems that the MT-MMP-1 expressions were increasing in proportion to Stromelysin-1 expressions. CONCLUSION: It is suggested that Stromelysin-1 and MT-MMP-1 may be partly involved in the progression of periodontal inflammation associated with type 2 DM, as related to a metabolism of other factors, such as AGE, plasmin and other inflammatory mediators. Therefore, the expression levels of Stromelysin-1 and MT-MMP-1 can be inflammatory markers of periodontal inflammed tissue with type 2 DM.

Microglia, major player in the brain inflammation: their roles in the pathogenesis of Parkinson's disease

Inflammation, a self-defensive reaction against various pathogenic stimuli, may become harmful self-damaging process. Increasing evidence has linked chronic inflammation to a number of neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis. In the central nervous system, microglia, the resident innate immune cells play major role in the inflammatory process. Although they form the first line of defense for the neural parenchyma, uncontrolled activation of microglia may directly toxic to neurons by releasing various substances such as inflammatory cytokines (IL-1beta, TNF-alpha, IL-6), NO, PGE