Matrix metalloproteinase-9 and -7 are regulated in experimental autoimmune encephalomyelitis
Matrix metalloproteinase-9 and -7 are regulated in experimental autoimmune encephalomyelitis
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DOI：
10.1093/brain/121.1.159
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发表时间：
1998-01-01
期刊：
影响因子：
14.5
通讯作者：
Hartung, HP
中科院分区：
文献类型：
--
作者：
Kieseier, BC;Kiefer, R;Hartung, HP
基质金属蛋白酶（MMP）包括一组蛋白水解酶，其涉及神经系统的炎性疾病如多发性硬化症的发病机制。然而，MMPs在炎症神经系统中的确切功能和表达模式尚不清楚。在本研究中，我们研究了92-kDa明胶酶（MMP-9）的表达，从动物的脊髓过继转移实验性自身免疫性脑脊髓炎（AT-EAE），采用半定量竞争性逆转录-聚合酶链反应分析。MMP-9 mRNA水平升高，在疾病严重程度最高时达到峰值。mRNA表达的增加与这种酶的蛋白水解活性增强有关，如明胶酶谱所示。免疫组化显示免疫反应沿着脑膜，血管周围和实质内，在患病的但不是在正常的脊髓。此外，研究了其他五种MMPs的表达模式。还发现基质溶素（MMP-7）在疾病高峰时以最大mRNA水平上调。相比之下，胶原酶-3，72-kDa明胶酶和基质溶解素-1和-3的mRNA没有变化。我们的研究结果表明，92-kDa明胶酶和基质溶解素选择性上调AT-EAE期间，因此可能有助于中枢神经系统炎症性疾病的发病机制。
Matrix metalloproteinases (MMPs) comprise a group of proteolytic enzymes that are implicated in the pathogenesis of inflammatory diseases of the nervous system such as multiple sclerosis. However; the exact function and expression pattern of MMPs in the inflamed nervous system are not known. In the present study we investigated the expression of 92-kDa gelatinase (MMP-9) in spinal cord from animals with adoptive transfer experimental autoimmune encephalo myelitis (AT-EAE), using a semiquantitative competitive reverse transcriptase-polymerase chain reaction assay. Increased level's of MMP-9 mRNA were found with peak values at times of maximum disease severity. Increased mRNA expression was associated with enhanced proteolytic activity of this enzyme, as demonstrated by gelatin zymography. Immunohistochemistry revealed immunoreactivity along the meninges, around blood vessels and within the parenchyma, in diseased bur not in normal spinal cord. Furthermore, the expression pattern of five other MMPs was investigated. Matrilysin (MMP-7) was also found to be upregulated with maximum mRNA levels at the peak of the disease. In contrast, mRNAs for collagenase-3, 72-kDa gelatinase, and stromelysin-1 and -3 were not changed. Our findings indicate that 92-kDa gelatinase and matrilysin are selectively upregulated during AT-EAE and thus may contribute to the pathogenesis of inflammatory diseases of the CNS.