Induction of host matrix metalloproteinases by Borrelia burgdorferi differs in human and murine Lyme arthritis
Induction of host matrix metalloproteinases by Borrelia burgdorferi differs in human and murine Lyme arthritis
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DOI：
10.1128/iai.73.1.126-134.2005
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发表时间：
2005-01-01
影响因子：
3.1
通讯作者：
Hu, LT
中科院分区：
文献类型：
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作者：
Behera, AK;Hildebrand, E;Hu, LT
基质金属蛋白酶 (MMP) 是由宿主组织响应伯氏疏螺旋体诱导产生的。 MMP 的上调可能在生物体通过细胞外基质组织的传播中发挥作用，但它也可能导致破坏性病理。尽管小鼠是公认的莱姆关节炎模型，但与人类疾病相比仍存在显着差异。我们试图确定 MMP 表达是否可以解释其中一些差异。通过使用基因阵列、实时 PCR、酶联免疫吸附测定和免疫组织化学，分析了原代人软骨细胞、莱姆关节炎患者的滑液样本以及莱姆关节炎易感和耐药小鼠的软骨组织中伯氏疏螺旋体感染后的 MMP 表达模式。伯氏疏螺旋体感染显着诱导原代人软骨细胞转录 MMP-1、-3、-13 和 -19。随着伯氏疏螺旋体感染，MMP-10 和金属蛋白酶 I 组织抑制剂的转录增加，但蛋白质表达仅略有增加。高螺旋体负荷和低螺旋体负荷患者的滑液中 MMP 水平与体外研究结果一致。感染伯氏疏螺旋体的伯氏疏螺旋体易感的C3H/HeN小鼠表现出MMP-3和MMP-19的诱导，但没有其他MMP或金属蛋白酶的组织抑制剂。免疫组织化学测定发现，MMP-3 表达仅在靠近关节面的软骨细胞中增加。在莱姆关节炎抵抗力更强的 BALB/c 和 C57BL/6 小鼠中，MMP 水平显着降低。人类和小鼠莱姆关节炎之间的差异可能与小鼠关节中缺乏胶原酶（例如 MMP-1 和 MMP-13）的诱导有关。
Matrix metalloproteinases (MMPs) are induced from host tissues in response to Borrelia burgdorferi. Upregulation of MMPs may play a role in the dissemination of the organism through extracellular matrix tissues, but it can also result in destructive pathology. Although mice are a well-accepted model for Lyme arthritis, there are significant differences compared to human disease. We sought to determine whether MMP expression could account for some of these differences. MMP expression patterns following B. burgdorferi infection were analyzed in primary human chondrocytes, synovial fluid samples from patients with Lyme arthritis, and cartilage tissue from Lyme arthritis-susceptible and -resistant mice by using a gene array, real-time PCR, an enzyme-linked immunosorbent assay, and immunohistochemistry. B. burgdorferi infection significantly induced transcription of MMP-1, -3, -13, and -19 from primary human chondrocyte cells. Transcription of MMP-10 and tissue inhibitor of metalloprotease I was increased with B. burgdorferi infection, but protein expression was only minimally increased. The synovial fluid levels of MMPs from patients with high and low spirochete burdens were consistent with results seen in the in vitro studies. B. burgdorferi-susceptible C3H/HeN mice infected with B. burgdorferi showed induction of MMP-3 and MMP-19 but no other MMP or tissue inhibitor of metalloprotease. As determined by immunohistochemistry, MMP-3 expression was increased only in chondrocytes near the articular surface. The levels of MMPs were significantly lower in the more Lyme arthritis-resistant BALB/c and C57BL/6 mice. Differences between human and murine Lyme arthritis may be related to the lack of induction of collagenases, such MMP-1 and MMP-13, in mouse joints.