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基质金属蛋白酶-2 和 -9 导致感染弓形虫的星形胶质细胞中纤维连接蛋白的降解。

Matrix metalloproteinase-2 and -9 lead to fibronectin degradation in astroglia infected with Toxoplasma gondii.

机构信息

Institue of Medicine, Chung Shan Medical University, Taichung, Taiwan.

出版信息

Acta Trop. 2013 Mar;125(3):320-9. doi: 10.1016/j.actatropica.2012.11.002. Epub 2012 Nov 29.

DOI:10.1016/j.actatropica.2012.11.002
PMID:23201304
Abstract

Toxoplasma gondii is a zoonotic parasite and its infection in human can induce toxoplasmic encephalitis in immune disorders. In this study, astroglia were infected with the TS-4 strain of T. gondii tachyzoite in vitro to investigate the changes of matrix metalloproteinase (MMP)-2, MMP-9 and their substrate fibronectin. MMP-2 and MMP-9 were significantly increased at 1 h, 6 h and 12 h post-infection (PI) in the cell homogenates, and increased at 6 h, 12 h, 24 h and 48 h PI in the cell-cultured supernatants. Fibronectin degradation also occurred at the same time points. In addition, immunocytochemistry showed that MMP-2 and MMP-9 localized in the cytoplasm, and confocal scanning laser microscopy revealed co-labeled patterns of MMP-2 and MMP-9 with fibronectin. MMP-2 and MMP-9 interacted with fibronectin, respectively. These results suggest that MMP-2 and MMP-9 induction from astroglia may contribute to extracellular matrix (ECM) degradation occurring in toxoplasmosis. Thus, we hypothesize that MMP-2 and MMP-9 cleave fibronectin and may contribute to the astroglia reaction and leukocyte migration to the sites of T. gondii replication during toxoplasmic encephalitis.

摘要

刚地弓形虫是一种动物源性寄生虫,其感染人类可导致免疫功能紊乱患者发生弓形体脑炎。在本研究中,体外感染星形胶质细胞 TS-4 速殖子株,探讨基质金属蛋白酶(MMP)-2、MMP-9 及其底物纤维连接蛋白的变化。细胞匀浆中 MMP-2 和 MMP-9 在感染后 1 h、6 h 和 12 h 明显增加,细胞培养上清液中 MMP-2 和 MMP-9 在感染后 6 h、12 h、24 h 和 48 h 增加。同时也发生了纤维连接蛋白的降解。此外,免疫细胞化学显示 MMP-2 和 MMP-9 定位于细胞质,共聚焦扫描激光显微镜显示 MMP-2 和 MMP-9 与纤维连接蛋白的共标记模式。MMP-2 和 MMP-9 分别与纤维连接蛋白相互作用。这些结果表明,星形胶质细胞中 MMP-2 和 MMP-9 的诱导可能导致弓形体病中细胞外基质(ECM)的降解。因此,我们假设 MMP-2 和 MMP-9 裂解纤维连接蛋白,可能有助于弓形体脑炎时星形胶质细胞反应和白细胞向弓形虫复制部位迁移。

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