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首页> 外文期刊>Microbes and infection >Differential regulation of gelatinase A and B and TIMP-1 and -2 by TNFalpha and HIV virions in astrocytes.
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Differential regulation of gelatinase A and B and TIMP-1 and -2 by TNFalpha and HIV virions in astrocytes.

机译：星形胶质细胞中TNFalpha和HIV病毒粒子对明胶酶A和B以及TIMP-1和-2的差异调节。

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摘要

Changes in the fine balance between matrix metalloproteinases and their tissue inhibitors, which drives extracellular matrix turnover, may be critical to central nervous system inflammation in HIV infection as well as in neurotoxicity. Although they do not produce virus when infected by HIV, astrocytes may be directly affected by the virion, because some viral proteins are known to transduce signaling in brain cells and are also sensitive to the major proinflammatory cytokine TNFalpha. We therefore studied the effects of HIV and TNFalpha on MMP-2, MMP-9 and their inhibitors, TIMP-1 and TIMP-2, in astrocytes, by zymography and ELISA, respectively, or by RT-PCR for both of them. HIV slightly increased the production of pro-MMP-2 and pro-MMP-9 by astrocytes, in a dose-dependent manner. TNFalpha strongly induced pro-MMP-9. TIMP-1 and TIMP-2 levels were affected only slightly, if at all, by HIV and TNFalpha. Thus, astrocyte/HIV contact may lead to extracellular matrix activation, which may be strongly amplified by the inflammatory response. Our data strongly suggest that, besides their physiological production of MMP-2, astrocytes would be a major source of MMP-9 in the inflamed brain.
机译：基质金属蛋白酶及其组织抑制剂之间精细平衡的变化，这会驱动细胞外基质更新，可能对HIV感染中的中枢神经系统炎症以及神经毒性至关重要。尽管星形胶质细胞在被HIV感染时不会产生病毒，但它们可能会直接受到病毒体的影响，因为已知某些病毒蛋白会在脑细胞中转导信号，并且对主要的促炎性细胞因子TNFα敏感。因此，我们分别通过酶谱法和ELISA或通过RT-PCR研究了HIV和TNFα对星形胶质细胞中MMP-2，MMP-9及其抑制剂TIMP-1和TIMP-2的影响。 HIV以剂量依赖的方式稍微增加了星形胶质细胞产生的pro-MMP-2和pro-MMP-9。 TNFalpha强烈诱导MMP-9。 HIV和TNFalpha对TIMP-1和TIMP-2的水平影响甚微。因此，星形胶质细胞/ HIV的接触可能会导致细胞外基质的激活，其可能会被炎症反应强烈放大。我们的数据强烈表明，除了生理上产生MMP-2外，星形胶质细胞将是发炎脑中MMP-9的主要来源。

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