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Serum Levels Of Matrix Metalloproteinase-9 (MMP-9) And Tissue Inhibitor Of Metalloproteinase-1 (TIMP-1) In Patients With Systemic Lupus Erythematosus And Their Clinical Significances

Posted on:2004-06-21Degree:MasterType:Thesis
Country:ChinaCandidate:W H YinFull Text:PDF
GTID:2144360092990652Subject:Dermatology and Venereology
Abstract/Summary:PDF Full Text Request
Matrix metalloproteinases (MMPs) are members of a family of Zn-dependent endopeptidases that are responsible for degradation of various protein components of the extracellular matrix (ECM). The activity of MMPs is controlled by the tissue inhibitors of metalloproteinases (TIMPs), which inhibit active MMPs by binding in a 1 : 1 molar ratio to form tight non-covalent complexes. The balance between MMPs and TIMPs play an important role in physiological and pathological processes, including embryonic development, pregnancy and parturition, extracellular matrix turnover, tissue remodeling and repair, inflammatory reaction, tumor invasion and metastasis. Of the MMPs family, matrix metalloproteinase-9 (MMP-9) is the largest and most complex member identified so far, which can degrade type IV, V, VII, X and XI collagens, fibronectin, laminin, vitronectin aggrecan, gelatin and elastin. The specific inhibitor of MMP-9 is the tissue inhibitor of metalloproteinase-1 (TIMP-1).MMP-9 is synthesized and secreted by neutrophils, macrophages, flbroblasts and endotheliocytes. It play an important role in migration of inflammatory cells and invasion of tumor cells by degrade the basement membranes.Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the increased production of a broad spectrum of autoantibodies against several self-antigens and immune complexes depositions in the kidneys and other organs. The latter are associated with the infiltration of leucocyte and production of inflammatory reaction. The cause of the disease has not yet been defined yet. The infiltration of inflammatory cells, vascular lesions and abnormality of ECM metabolism have been shown to be involved in lupus nephritis. The involvement of MMPs in autoimmune diseases has been demonstrated in multiple sclerosis, rheumatoid arthritis, experimental bullous pemphigoid and experimental autoimmune neuritis. Thus, MMP-9 and TIMP-1 may also play a role in the pathogenesis of SLE. In this study, serum levels of MMP-9 and TIMP-1 in 46 patients with SLE and 30 healthy controls were measured, and their clinical significances were discussed in this paper.Materials and methods1. Clinical dataThirty healthy controls and forty-six patients with SLE were evaluated in this study. All patients fulfilled the American Rheumatism Association 1982 revised criteria for the diagnosis of SLE. The patients included 42 females and 4 males whose age ranged from 11 to 61 with an average of 30.91 ± 13.90 (SD) years, duration from 15 days to 30 years. Eleven serum samples were collected from patients taking corticosteroid after three or four weeks. The healthy controls included 27 females and 3 males whose age ranged from 21 to 40 with an average of 30.57 ± 5.55(SD) years. The age and sex of healthy controls matched that of the patients.Disease activity of patients with SLE was evaluated using the SLEDAI standard. Active SLE was defined according to the Zhengmin's criteria, and renal lupus was confirmed by urine analysis (proteinuria higher than 500mg/24h).2. Laboratory studiesThe serum samples were stored at -70℃ until use. Serum levels of MMP-9 and TIMP-1 were measured by enzyme-linked immunosorbent assay (ELISA). ELISA kits for MMP-9 and TIMP-1 were purchased from R&D systems Inc. Assays were performed according to the manufacturer's instructions.3. Statistical analysisAll data analyses were performed using SPSS 10.0 software. Because serum levels of MMP-9 and TIMP-1 did not follow a Gaussian distribution, results are expressed as median values with the 25 - 75 centiles (interquartile range). Between group differences were analysed with the non-parametric Mann-Whitney U test. The Wilcoxon rank sum test was used to compare paired groups. Correlations were determined by Spearman's rank order correlation and linear regression after logarithmic transformation. P values of less than 0.05 were considered significant.Results1. Serum levels of MMP-9 and TIMP-1 in patients with SLE and healthy controls1)...
Keywords/Search Tags:Lupus erythematosus, systemic, Matrix metalloproteinase-9, Tissue inhibitor of metalloproteinase-1
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