Synovial MMP-3 and TIMP-1 levels and their correlation with cytokine expression in canine rheumatoid arthritis

Synovial MMP-3 and TIMP-1 levels and their correlation with cytokine expression in canine rheumatoid arthritis
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DOI:
10.1016/s0165-2427(03)00005-9
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发表时间:
2003-02-10
影响因子:
1.8
通讯作者:
Schmidt, MFG
Schmidt, MFG
中科院分区:
农林科学3区
文献类型:
--
作者:
Hegemann, N;Wondimu, A;Schmidt, MFG

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本研究旨在探讨类风湿关节炎(CRA)犬关节滑液中基质金属蛋白酶-3(MMP3)和金属蛋白酶组织抑制因子-1(TIMP-1)的表达水平是否与骨关节病相比有特异性的升高,以及这些标志物是否与特定的细胞因子基因表达模式相关。逆转录-聚合酶链式反应(RT-PCR)检测滑膜组织中肿瘤坏死因子-α(TNF-α)、白介素1(IL-1)、白介素6(IL-6)、白介素12(IL-12)、转化生长因子-β(TGF-β)、干扰素-γ(IFN-γ)的mRNA含量。以前交叉韧带断裂(ACLR)所致的骨性关节炎犬(n=50)为对照,发现CRA关节滑液中的基质金属蛋白酶-3(MMP3)显著升高,而足量的TIMP-1不能使其平衡。滑膜组织中IL-1、IL-12和TGF-β的表达水平与滑膜组织中MMP3和TIMP-1的表达水平呈正相关。我们的结果表明,滑膜中的基质金属蛋白酶-3水平可能被用来作为犬类风湿关节炎的标志物。(C)2003年,爱思唯尔科学公司出版。
The purpose of this study was to investigate whether synovial fluid levels of matrix metalloprotease-3 (MMP-3) and tissue inhibitor of metalloprotease-1 (TIMP-1) are specifically elevated in canine rheumatoid arthritis (CRA) compared to osteoarthritic joint disorders and if these markers are correlated with a specific pattern of cytokine mRNA expression.Synovial fluid samples of 17 dogs with CRA were analysed for MMP-3 and TIMP-1 by two canine sandwich ELISA (enzyme-linked immunosorbent assay) systems. The synovial mRNA content of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-12 (IL-12), transforming growth factor-beta (TGF-beta), and interferon-gamma (IFN-gamma) was determined by RT-PCR (reverse transcription-polymerase chain reaction). Dogs with osteoarthritis (n = 50) caused by anterior cruciate ligament rupture (ACLR) were used as controls.A significant rise of MMP-3 was found in the synovial fluid of joints with CRA that could not be balanced by sufficient amounts of TIMP-1. The 30-fold surplus of MMP-3 over TIMP-1 was strongly correlated with the synovial mRNA content of IL-1, IL-12 and TGF-beta. Our results point to the potential use of the synovial levels of MMP-3 as a marker for RA in dogs. (C) 2003 Published by Elsevier Science B.V.