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The induction of matrix metalloproteinase and cytokine expression in synovial fibroblasts stimulated with immune cell microparticles.

ABSTRACT: Rheumatoid arthritis is a chronic inflammatory disease characterized by destruction of cartilage and bone that is mediated by synovial fibroblasts. To determine the mechanisms by which these cells are activated to produce matrix metalloproteinases (MMPs), the effects of microparticles were investigated. Microparticles are small membrane-bound vesicles whose release from immune cells is increased during activation and apoptosis. Because microparticles occur abundantly in the synovial fluid in rheumatoid arthritis, they could represent novel stimulatory agents. Microparticles derived from T cells and monocytes strongly induced the synthesis of MMP-1, MMP-3, MMP-9, and MMP-13 in fibroblasts. The induction was time-dependent, with effects primarily observed after 36 h; under these conditions, MMP-2, MMP-14, and tissue inhibitor of MMP-1 (TIMP-1), TIMP-2, and TIMP-3 were not induced. Microparticles also increased the synthesis of inflammatory mediators including IL-6, IL-8, monocyte chemoattractant protein 1 (MCP-1), and MCP-2. In Ikappa-B-transfected synovial fibroblasts, MMPs were less inducible by microparticles compared with wild-type fibroblasts. Blocking of TNFalpha and IL-1beta with antibodies against TNFalpha and with IL-1 receptor antagonist did not abrogate stimulation by microparticles. These data provide evidence for a novel mechanism by which vesicles derived from activated or apoptotic immune cells can promote the destructive activity of synovial fibroblasts in rheumatoid arthritis.

SUBMITTER: Distler JH

PROVIDER: S-EPMC548330 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionMetalloproteinases-3 (MMP3) are the main enzymes involved in cartilage degradation. Several genetic and non-genetic factors can increase the expression of MMP3 in patients with osteoarthritis (OA). This study aims to analyze the risk factors associated with the expression of the MMP3 gene rs679620 fluid synovial knee OA patients.MethodsA cross-sectional study was conducted at the orthopedic polyclinic Arifin Achmad Riau Province and Ibn Sina Hospital in Pekanbaru City. Ninety women who experienced knee OA were taken as samples by consecutive sampling and then signed the informed consent. Data were obtained through interviews using a questionnaire about characteristics, followed by weight and height measurements. Interleukin-1 β (IL-1β) and Tumor Necrosis Factor (TNF-α) were examined from the synovial fluid using the enzyme-linked immunosorbent assay (ELISA) method. The Metalloproteinases-3 (MMP3) gene polymorphism rs679620 was obtained from the DNA analysis of joint fluid results in the Biomedical Laboratory of the Faculty of Medicine, Andalas University. The data was processed computerized and then analyzed using the correlation Spearman-Rank, and chi-square tests. The results of statistical analysis are considered significant if the p-value is 0.05.ResultsThe MMP3 rs679620 gene polymorphism of the mutant type was 88.9%, with the same proportion of AG and GG alleles (44.4%). Subjects aged ≥ 60 years were 53.3%, 85.6% did not work and 84.4% had menopause. The highest degree of OA was grade 2 (53.3%), most of whom had a risky nutritional status (84.4%). The median expression of the MMP3 rs679620 gene was 5.28 copies number. There is a significant relationship between MMP3 gene polymorphism rs679620, age, IL-1β, and TNF-α with MMP3 gene expression rs679620. There is no significant relationship between BMI, work status, and menopausal status with MMP3 gene expression rs679620. Conclusion. MMP3 gene polymorphism rs679620, age, levels of IL-1β and TNF-α are risk factors for increased MMP3 gene rs679620 expression in female knee OA.

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The induction of matrix metalloproteinase and cytokine expression in synovial fibroblasts stimulated with immune cell microparticles.

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