Anti-tumour necrosis factor (TNF)-α therapy (etanercept) down-regulates serum matrix metalloproteinase (MMP)-3 and MMP-1 in rheumatoid arthritis
Anti-tumour necrosis factor (TNF)-α therapy (etanercept) down-regulates serum matrix metalloproteinase (MMP)-3 and MMP-1 in rheumatoid arthritis
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DOI：
10.1093/rheumatology/41.5.484
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发表时间：
2002-05-01
期刊：
影响因子：
5.5
通讯作者：
Ulfgren, AK
中科院分区：
文献类型：
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作者：
Catrina, AI;Lampa, J;Ulfgren, AK
目标。基质金属蛋白酶（MMPs）是细胞因子调节酶，通过诱导骨吸收和软骨破坏在类风湿关节炎（IRA）的发病机制中起重要作用。本研究评估了可溶性肿瘤坏死因子(TNF) α受体（依那西普）治疗对血清和滑膜MMPs及其抑制剂基质金属蛋白酶(TIMP)-1组织抑制剂的调节作用。在基线和治疗8周或12周后收集60例RA患者的血清样本。在治疗前和8周后的两个时间点对11名患者进行了成对的滑膜活检。采用ELISA法检测血清MMP-1、MMP-3、TIMP-1水平。采用MMP-1、MMP-3和timp -1特异性单克隆抗体对滑膜组织进行免疫组织学分析。依那西普治疗显著降低RA患者血清MMP-3和MMP-1水平，同时降低炎症参数（c反应蛋白浓度和红细胞沉降率）。基线预处理血清MMP-3水平与治疗期间临床疾病活动度的变化相关。依那西普治疗后，血清中TIMP-1水平无一致性变化，而MMP-1和MMP-3与TIMP-1的比值下调。免疫组织化学分析显示个体间差异很大，通常MMP表达水平高，TIMP表达水平低。在治疗过程中，阳性细胞的形态或数量未发生明显变化。在RA患者中，依那西普治疗可下调血清中MMP-3和MMP-1的水平以及mmp与TIMP-1的比值。这可能是预防关节损伤未来发展的重要机制。
Objectives. Matrix metalloproteinases (MMPs) are cytokine-modulated enzymes that play an important role in the pathogenesis of rheumatoid arthritis (IRA.) by inducing bone resorption and cartilage destruction. This study evaluated the modulation of serum and synovial MMPs and their inhibitor, tissue inhibitor of matrix metalloproteinases (TIMP)-1, by therapy with soluble tumour necrosis factor (TNF) alpha receptor (etanercept).Methods. Serum samples were collected from 60 RA patients at baseline and after 8 or 12 weeks of treatment. Paired synovial biopsies were obtained from 11 patients at two time points, before and after 8 weeks of treatment. We measured serum levels of MMP-1, MMP-3 and TIMP-1 by ELISA. Immunohistological analysis of synovial tissue Was performed using monoclonal antibodies specific For MMP-1, MMP-3 and TIMP-1.Results. Etanercept therapy significantly down-regulated Serum levels of MMP-3 and MMP-1 in parallel with the reduction in inflammatory parameters (C-reactive protein concentration and erythrocyte sedimentation rate) in RA patients. Baseline pretreatment serum levels of MMP-3 correlated with changes in clinical disease activity during therapy. No consistent changes in serum level of TIMP-1 were observed, while ratios of MMP-1 and MMP-3 to TIMP-1 were down-regulated following etanercept treatment. Immunohistochemical analyses revealed great interindividual variability, with generally a high level of expression of MMP and low expression of TIMP. No significant change in the pattern Or number of positive cells occurred during therapy.Conclusions. In RA patients, etanercept therapy down-regulates serum levels of MMP-3 and MMP-1 and the ratio between MMPs and TIMP-1. This may be an important mechanism for the prevention of future development of joint damage.