Clinical Immunology and Immunopathology
Regular ArticleMarkedly Elevated Serum MMP-9 (Gelatinase B) Levels in Rheumatoid Arthritis: A Potentially Useful Laboratory Marker
Abstract
In an attempt to find a potentially useful serum marker in rheumatoid arthritis (RA) which reflects underlying pathogenic mechanisms, we measured the circulating levels of matrix-degrading metalloproteinase-9 (MMP-9), also termed gelatinase B, in sera and synovial fluid (SF) from patients with RA and also quantitated the deposition and local synthesis of MMP-9 in RA synovium. Clinical samples, subjected to gelatin substrate zymography, antigenic immunoassay, and a quantitative substrate degradation assay, revealed elevated 92- and 72-kDa proenzyme forms of MMP-9 and MMP-2 in RA sera and SF compared with healthy controls. Immunostaining on fresh RA synovial specimens revealed MMP-9 within vascular walls in fibroblast-like cells and macrophages; mRNA synthesis was detected using reverse transcriptasein situPCR. In summary, MMP-9 levels are substantially elevated in the sera and SF from patients with RA. The RA synovium is a source of this MMP-9 production, with abundant mRNA and protein observed within several different type of rheumatoid synovial cells.
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Phillyrin ameliorated collagen-induced arthritis through inhibition of NF-κB and MAPKs pathways in fibroblast-like synoviocytes
2023, Arabian Journal of ChemistryThe discovery of alternative medicines with less adverse effects is extremely urgent for rheumatoid arthritis (RA). Phillyrin (Phil), the predominant lignan glycoside of Forsythia suspensa, has been reported to exert several pharmacological effects, such as antivirus, anti-inflammation, anti-oxidation, anti-obesity, and antipyretic activity. However, the effect of Phil on RA remains unknown. In this study, We utilized both in vivo collagen-induced arthritis (CIA) rat models and in vitro TNFα-induced fibroblast-like synoviocytes (FLSs) to study the inhibitory effects of Phil on RA. The in vivo studies revealed that Phil treatment effectively ameliorated synovial inflammation and bone erosion in CIA rats. The in vitro studies demonstrated that Phil could significantly suppress the proliferation and migration of arthritic FLSs. In addition, treatment with Phil resulted in decreased mRNA expression of proinflammatory cytokines including TNFα, IL-1β, IL-6, IL-8 and MMP9. Molecular mechanistic investigations revealed that the suppressive effects of Phil were mediated by blockade of the MAPK (ERK, p38, and JNK) and NF-κB pathways. Taken together, our findings suggest that Phil has an anti-arthritic effect in CIA rats by inhibiting the pathogenic characteristic of arthritic FLSs throught suppression of NF-κB and MAPKs signaling pathways. These results demonstrate the potential of Phil as a novel therapeutic agent for the treatment of RA.
Involvement of matrix metalloproteinases and their inhibitors in Staphylococcus aureus chronically infected bovine mammary glands during active involution
2021, Research in Veterinary ScienceThe aim of this study was to characterize the protein expression of matrix metalloproteinase-2 (MMP-2) and ‐− 9 and their inhibitors (TIMP-1 and -2) in mammary tissue of dairy cows with naturally occurring chronic S. aureus intramammary infections (IMI) during active involution. Moreover, the gelatinolytic activity of MMP-2 and -9 in mammary secretions was evaluated. Cows in late lactation that were either uninfected or with chronic naturally acquired S. aureus IMI were included in this study. Protein expression of MMP-2 and -9 in mammary tissues was significantly higher in S. aureus-infected than uninfected quarters at day 14 and 21 of involution. Protein expression of TIMP-1 and -2 was significantly higher in S. aureus-infected than uninfected quarters at day 7, 14 and 21 of involution. The MMP-2/TIMP-1, MMP-2/TIMP-2, MMP-9/TIMP-1 and MMP-9/TIMP-2 ratios were significantly higher in S. aureus-infected compared with uninfected quarters at day 14 of involution. The MMP-2 activity was significantly higher in mammary secretions from S. aureus-infected compared with uninfected quarters at day 1, 2, 7 and 14 of involution. The MMP-9 activity was significantly higher in mammary secretions from infected quarters compared with uninfected quarters at day 7, 14 and 21 of involution. The increased expression of MMP-2 and -9 in mammary tissue as well as the high levels of activity observed in mammary secretion from infected quarters compared with uninfected quarters during active involution, strongly suggests that these gelatinases could contribute to degradation of mammary tissue components during chronic S. aureus IMI. The MMPs/TIMPs imbalance could lead to greater proteolysis and potentially more damage to mammary tissue in S. aureus-infected quarters.
Protease activity and protein profile in milk from healthy dairy cows and cows with different types of mastitis
2019, International Dairy JournalMastitis in dairy cattle has high morbidity and mortality rates, having serious consequences in milk production and quality. The aim of this work was to evaluate the activity of metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9) in milk from healthy dairy cattle and from cows with signs of clinical and subclinical mastitis. The levels of total proteins and proteases with caseinolytic activity were also evaluated. The highest caseinolytic activity was found in milk samples obtained from animals with mastitis, in which lower levels of casein, especially the κ-casein fraction, were found, as compared with healthy animals.
Enzymes as Diagnostic Tools
2019, Advances in Enzyme Technology, First EditionRapid and accurate diagnosis of critical diseases and their appropriate treatment are the primary factors that promote optimal clinical outcomes and general public health. Enzymes have remarkable biocatalytic properties, and because of this, they are extensively used in diagnostics of various diseases. Many enzymes are preferred markers for the detection of various diseases such as jaundice, myocardial infarction, neurodegenerative disorders, cancer, and so forth. Enzymes provide insights into various diseases by diagnosis, prognosis, and assessment of response therapy. Enzyme biosensors can also be used as an analytical tool for the diagnosis of widespread diseases. A number of enzyme biosensors have been constructed and used for the diagnosis of a wide assay of diseases. Despite clinical necessity, the commercialization of biosensors from research laboratories to the clinical diagnostics industry is still lacking, with a few exceptions, such as glucose, lactate, and cholesterol biosensors. This chapter describes the potential applications of enzymes, enzyme-based biosensors, and ELISA as diagnosis tools for various diseases.
Enzymes as diagnostic tools
2019, Biomass, Biofuels, Biochemicals: Advances in Enzyme TechnologyRapid and accurate diagnosis of critical diseases and their appropriate treatment are the primary factors that promote optimal clinical outcomes and general public health. Enzymes have remarkable biocatalytic properties, and because of this, they are extensively used in diagnostics of various diseases. Many enzymes are preferred markers for the detection of various diseases such as jaundice, myocardial infarction, neurodegenerative disorders, cancer, and so forth. Enzymes provide insights into various diseases by diagnosis, prognosis, and assessment of response therapy. Enzyme biosensors can also be used as an analytical tool for the diagnosis of widespread diseases. A number of enzyme biosensors have been constructed and used for the diagnosis of a wide assay of diseases. Despite clinical necessity, the commercialization of biosensors from research laboratories to the clinical diagnostics industry is still lacking, with a few exceptions, such as glucose, lactate, and cholesterol biosensors. This chapter describes the potential applications of enzymes, enzyme-based biosensors, and ELISA as diagnosis tools for various diseases.
Circulating matrix modulators (MMP-9 and TIMP-1) and their association with severity of diabetic retinopathy
2018, Diabetes and Metabolic Syndrome: Clinical Research and ReviewsDiabetic Retinopathy (DR) is the leading cause of vision loss in the working age population. Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1), are molecules involved in extracellular tissue matrix remodelling. They are implicated in the loss of retinal tissue integrity, a major cause of DR, that leads to retinal tissue degradation and apoptosis. This study is therefore, conducted to compare the serum levels of MMP-9 and TIMP-1 in T2DM patients without and with retinopathy, and to evaluate their association with the severity of DR.
Our study comprised of 2 groups of 41 each. Group A (cases) included T2DM patients with retinopathy and Group B (controls) included T2DM patients without retinopathy. Routine parameters, mainly, fasting blood glucose, and lipid profile were measured using autoanalyzer. Serum MMP-9, TIMP-1, and insulin levels were assessed using ELISA method.
Statistically significant increase in the levels of MMP-9, insulin, fasting blood glucose and lipid profile were observed in the serum of T2DM patients with retinopathy, as compared with those without retinopathy. These results help to conclude that rise in MMP-9, and associated serum markers promote disease progress in DR. These findings suggest that the elevations of our study markers in the serum of the type 2 diabetic patients with retinopathy, as compared to those without retinopathy, play important roles in aggravating tissue matrix degradation, supporting DR disease progression.
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