Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) have been reported to be associated with arthritis. Total joint replacement results in total resection of cartilage and synovium at the joint. We investigated longitudinal changes in plasma MMP and TIMP after total joint replacement. Eight patients with osteoarthritis (OA) and 15 patients with rheumatoid arthritis (RA) had total knee or total hip replacements. Plasma was collected from all patients before surgery and at 1 week and 6 weeks after surgery. In RA patients the plasma MMP-3 and the MMP-3/TIMP-1 ratio decreased after total joint replacement, whereas CRP and ESR did not change. Therefore, CRP and ESR reflect systemic inflammation; however, plasma MMP-3 and the MMP-3/TIMP-1 ratio may reflect inflammation and/or degeneration of the affected joint.
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PMID:Changes in the concentration of plasma matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases-1 (TIMP-1) after total joint replacement in patients with arthritis. 1244 32

We previously reported that follistatin-related protein (FRP)/TSC-36 was one of the target antigens of autoantibodies in rheumatoid arthritis (RA) and that the appearance of serum autoantibodies to FRP correlated to disease activity in RA. However, the significance of FRP in autoimmunity remained to be explained due to the unknown function of FRP. Here, we disclose in part the function of FRP. Transforming growth factor (TGF)-beta augmented FRP gene expression in synovial cells. FRP reduced synovial production of matrix metalloproteinase (MMP)-1, MMP-3 and prostaglandin E(2), potent agonists of joint destruction in RA. In contrast, autoantibodies to FRP from patients with RA increased their production by blocking FRP activity, probably in the autocrine system. Moreover, FRP down-regulated synovial expression of FOS (c-fos), which seemed responsible for the reduction in MMP-1 and MMP-3 caused by FRP. Therefore, FRP and its autoantibody can be regarded as defensive and offensive factors respectively in rheumatoid arthropathy. The major epitope of autoantibodies to FRP was mapped to the sequence LKFVEQNE (residues 169-176) and homologous sequences were found in proteins from Escherichia coli, Epstein-Barr virus, etc. FRP and its autoantibody may provide some clues to elucidate the process of disease development and a new approach to the design of therapeutics in RA.
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PMID:Potential preventive effects of follistatin-related protein/TSC-36 on joint destruction and antagonistic modulation of its autoantibodies in rheumatoid arthritis. 1250 27

Matrix metalloproteinase-3 is abundantly expressed in active rheumatoid synovium, and serum level of MMP-3 is a useful marker not only for the diagnosis of rheumatoid arthritis but also for the evaluation of prognosis in the joint destruction. It should be noted, however, that serum MMP-3 may be increased in other inflammatory arthritis, thus its specificity for the diagnosis of early RA may not be high enough. Recent reports indicated that methotrexate or anti-TNF alpha therapy effectively suppressed the serum MMP-3 level during the course of the treatment, whereas corticosteroid didn't. Thus, suppression of serum MMP-3 could explain the discrepancy in the inhibition of bony destruction in RA patients by the therapeutic strategy.
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PMID:[Usefulness of serum matrix metalloproteinase-3(MMP-3) level in the diagnosis of rheumatoid arthritis]. 1251 Mar 57

During the pathogenesis of rheumatoid arthritis (RA), the synovial fibroblasts increase in number and produce proinflammatory cytokines and matrix metalloproteinases (MMPs) that function to promote inflammation and joint destruction. Recent investigations have suggested that cell cycle activity and inflammation may be linked. However, little is known about the mechanisms responsible for the coordinate regulation of proliferation and the expression of proinflammatory molecules in RA synovial fibroblasts. Here, we demonstrate a 50 +/- 10% decrease in the expression of p21, a cell cycle inhibitor, in the synovial fibroblast population from RA compared with osteoarthritis (OA) synovial tissue. Moreover, p21 positivity in the synovial fibroblasts inversely correlates with medium synovial lining thickness (r = -0.76; p < 0.02). The expression of p21 is also reduced in isolated RA synovial fibroblasts compared with OA synovial fibroblasts. Adenovirus-mediated delivery of p21 (Ad-p21) arrests both RA and OA synovial fibroblasts in the G(0)/G(1) phase of the cell cycle without inducing cytotoxicity. However, the spontaneous production of IL-6 and MMP-1 is suppressed only in the Ad-p21-infected RA synovial fibroblasts, indicating a novel role for p21 in RA. Analyses of p21-deficient mouse synovial fibroblasts reveal a 100-fold increase in IL-6 protein and enhance IL-6 and MMP-3 mRNA. Restoration of p21, but not overexpression of Rb, which also induces G(0)/G(1) cell cycle arrest, decreases IL-6 synthesis in p21-null synovial fibroblasts. Furthermore, in RA synovial fibroblasts the ectopic expression of p21 reduces activation of the AP-1 transcription factor. Additionally, p21-null synovial fibroblasts display enhanced activation of AP-1 compared with wild-type synovial fibroblasts. These data suggest that alterations in p21 expression may activate AP-1 leading to enhanced proinflammatory cytokine and MMP production and development of autoimmune disease.
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PMID:IL-6 and matrix metalloproteinase-1 are regulated by the cyclin-dependent kinase inhibitor p21 in synovial fibroblasts. 1251 48

We determined serum metalloproteinase-3(MMP-3) and inflammatory cytokine(IL-6, IL-8) levels in patients with rheumatoid arthritis(RA). Sera were obtained from 307 healthy subjects(female 140, male 167), 54 RA patients, and 17 osteoarthritis (OA). The MMP-3 concentrations in healthy female and male were 43.3 +/- 15.3 ng/ml and 90.7 +/- 26.0 ng/ml, respectively. The serum MMP-3 levels in male were significantly higher than those in female (p < 0.0001). MMP-3 levels in RA patients(259.1 +/- 34.2 ng/ml) were significantly higher than OA(43.6 +/- 6.1 ng/ml) or healthy controls. There was a significant correlation between MMP-3 and CRP(r = 0.586), IL-6(r = 0.345) levels in serum. In contrast, no significant correlation was observed between MMP-3 and IL-8(r = 0.19), or CA-RF(r = 0.052) levels. However, there were some cases with high MMP-3 levels in CA-RF-negative patients definitely diagnosed as RA. These findings suggest that MMP-3 determination is useful for the early diagnosis and the follow-up during the treatment for RA patients.
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PMID:[Clinical significance of MMP-3 in patients with rheumatoid arthritis: comparison with other inflammatory markers(IL-6, IL-8)]. 1265 86

We explored whether the serum concentration of interleukin 6 (IL-6) is associated with matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in rheumatoid arthritis (RA) patients. Serum levels of IL-6, interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase B (MMP-9), TIMP-1 and TIMP-2 were assessed with an ELISA technique in 30 RA patients. We observed the association between IL-6 and MMP-1 (p < 0.001), MMP-3 (p < 0.05), MMP-9 (p < 0.001), TIMP-1 (p < 0.01) and TIMP-2 (p < 0.05). Additionally, serum IL-6, measured MMPs and TIMP-1 correlated with the erythrocyte sedimentation rate, C reactive protein plasma level and the number of swollen joints. We suggest that assessing the serum IL-6, MMP-1, MMP-3, MMP-9 and TIMP-1 levels may be helpful in the prediction of the RA activity.
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PMID:[Serum interleukin 6 (il-6A) concentration correlates with matrix metalloproteinases and their tissue inhibitors in rheumatoid arthritis]. 1287 74

Tumour necrosis factor alpha (TNF-alpha) and matrix metalloproteinases (MMPs) play an important role in the pathogenesis of rheumatoid arthritis (RA). The present study was conducted to investigate whether the serum level of TNF-alpha is correlated with MMPs and tissue inhibitors of metalloproteinases (TIMPs) in RA patients. Serum concentrations of TNF-alpha, interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase B (MMP-9), TIMP-1 and TIMP-2 were measured by ELISA in 34 patients with RA. We found the TNF-alpha to correlate with MMP-1, MMP-3, MMP-9 and total measured MMPs serum concentrations (p < 0.05 for all comparisons). Furthermore, serum TNF-alpha, MMP-1 MMP-3, MMP-9 and TIMP-1 levels correlated with markers of disease activity such as the erythrocyte sedimentation rate, C reactive protein level and the number of swollen joints. No associations were observed between TNF-alpha and TIMPs serum concentrations. Our results support the concept of the regulation of the MMPs synthesis by cytokines such as TNF-alpha. We conclude that the measurement of the serum TNF-alpha, MMPs and TIMP-1 concentrations may be useful in the assessment of RA activity.
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PMID:[Correlation between tumor necrosis factor alpha and matrix metalloproteinases levels in serum of patients with rheumatic arthritis]. 1293 14

Qing-Luo-Yin (QLY), a traditional Chinese herbal medicine for the treatment of rheumatoid arthritis, is a combination of the extracts of Sophora flavescens Ait., Phellodendron amurense Rupr., Sinomenium acutum Rehd. et Wils. and Dioscorea hypoglauca Palib. The suppressive effect of QLY on the development of angiogenesis was investigated in a rat model of collagen-induced arthritis (CIA). QLY (0.3 g/kg) was orally administered daily for 27 days. Neo-angiogenesis, pannus and cartilage damage, the expression of metalloproteinases (MMP)-3 messenger RNA (mRNA) and the level of the tissue inhibitor of matrix metalloproteinase (TIMP)-1 in the synovium were examined by histology, in situ hybridization and immunohistochemiscal assays, respectively. It was observed that the articular morphological alterations, the over-expression of MMP-3 mRNA and the reduced production of TIMP-1 in CIA rats were significantly ameliorated by QLY. QLY performed about as effectively as tripterygium glycosidorum tablets (0.1 g/kg) extracted from Tripterygium wilfordii Hook. f.. These results indicate that QLY exerts a suppressive effect on the angiogenesis of CIA rats, and suggest that the therapeutic effect of QLY could be due to restoring the balance of MMP-3 and TIMP-1 in rheumatoid synovium.
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PMID:Suppressive effects of a Chinese herbal medicine qing-luo-yin extract on the angiogenesis of collagen-induced arthritis in rats. 1469 74

Matrix metalloproteinases (MMPs) are implicated in joint destruction in rheumatoid arthritis (RA). We investigated whether the 5A/6A polymorphism within the MMP-3 (stromelysin-1) gene promoter region is associated with disease outcome in 254 patients with established RA. Patients homozygous for the MMP-3 6A allele had more radiographic damage (measured by Larsen score) than those with other genotypes (109.8 vs 91.1, P=0.04). Patients with the 6A/6A genotype also had more functional impairment and higher serum proMMP-3 levels, although only the latter was significant (P=0.002). A possible association was found between homozygosity for the 6A allele and carriage of the RA-associated HLA-DRB1 shared epitope (SE). Combination of these factors was associated with more severe disease than the SE alone. The data suggest that the MMP-3 6A/6A genotype is associated with worse RA outcome, and that this genotype may have an additive effect with the SE on disease severity.
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PMID:Association of matrix metalloproteinase 3 promoter genotype with disease outcome in rheumatoid arthritis. 1471 11

Excessive production of interleukin-6 (IL-6) and metalloproteinases (MMPs) have been implicated in the pathogenesis of rheumatoid arthritis. Lipoxin A4 (LXA4) and transforming growth factor beta 2 (TGF-beta 2), mediators with potential anti-inflammatory activities, were tested to determine how they affect IL-1 beta-dependent release of IL-6 and MMPs in human fibroblast like synoviocytes. The results showed dramatic differences between the mediators: TGF-beta 2 acted synergistically with IL-1 beta to stimulate IL-6 protein levels, whereas LXA4 inhibited IL-6 expression in dose- and time-dependent manner. Inhibition, by LXA4 was abrogated when cells were pre-incubated with antibody against the LXA4R whereas TGF-beta 2 by itself had no significant effect on IL-6 or MMP levels. LXA4, at nanomolar concentrations, altered the MMP-1 and MMP-3 expression levels of IL-1 beta and TGF-beta 2 stimulated fibroblast like synoviocytes at 5 days. Furthermore, IL-1 beta and TGF-beta 2 up-regulated LXA4R mRNA. These results demonstrate, for the first time, that LXA4Rs mediate the effects of LXA4 on inflammatory responses after combined stimulation of human fibroblast like synoviocytes with IL-1 beta and TGF-beta 2. These activities might constitute an important mechanism by which LXA4 regulates human synovial fibroblast activation.
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PMID:Lipoxin A4 counteracts synergistic activation of human fibroblast-like synoviocytes. 1500 Aug 62


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