日本脑炎病毒感染 BALB/c 鼠脑中基质金属蛋白酶及其组织抑制剂的表达上调。
Upregulated expression of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in BALB/c mouse brain challenged with Japanese encephalitis virus.
机构信息
Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
出版信息
Neuroimmunomodulation. 2012;19(4):241-54. doi: 10.1159/000335182. Epub 2012 Mar 21.
BACKGROUND
Uncontrolled immune responses in the nervous system are potentially damaging following Japanese encephalitis virus (JEV) infection. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) act together to control the proteolysis of extracellular matrix. Disbalances in the MMP/TIMP system during virally induced neurodegenerative processes and inflammations are responsive to changes in the progression of diseases.
METHODS
The expression of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-3 in JEV-infected mouse brain was analyzed by RT-PCR for semiquantitation and ELISA for estimation of protein along with brain histopathology at different days postinoculation (dpi). Gelatin gel zymography was performed for MMP-2 and MMP-9 activities.
RESULTS
In the virus-infected group, expression of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-3 was found to be increased from 1 dpi to 6 dpi as compared to controls by both RT-PCR and ELISA. The expressions of MMPs and TIMPs at mRNA and protein levels were in concordance with each other. Post hoc multiple comparison analysis between days revealed that, in the virus-infected groups, significant increases (p < 0.05) in MMP and TIMP levels were observed between various dpi at both mRNA and protein levels. Only the MMP-7 protein level at 6 dpi was not significant compared to 5 dpi (p = 0.99).
CONCLUSION
Overexpression of MMPs and TIMPs is associated with disease severity in the central nervous system (CNS) during JEV infection. Our results showed that JEV infection can alter the expression of MMPs and TIMPs in the CNS. Thus, assessing these important immune mediators in CNS infection appears to play an important role in the development of symptoms and may help to understand the JEV-induced neurological disorders. More studies are required on this important enzymatic system to study their role in immune mediated pathogenesis.
背景
日本脑炎病毒（JEV）感染后，神经系统中失控的免疫反应可能具有破坏性。基质金属蛋白酶（MMPs）及其组织抑制剂（TIMPs）共同作用以控制细胞外基质的蛋白水解。病毒诱导的神经退行性过程和炎症中的 MMP/TIMP 系统失衡对疾病进展的变化有反应。
方法
通过 RT-PCR 进行半定量分析和 ELISA 进行蛋白估计，分析 JEV 感染小鼠脑中 MMP-2、MMP-7、MMP-9、TIMP-1 和 TIMP-3 的表达，并在接种后不同天数（dpi）进行脑组织病理学检查。进行明胶酶谱法测定 MMP-2 和 MMP-9 的活性。
结果
在病毒感染组中，与对照组相比，从 1 dpi 到 6 dpi，通过 RT-PCR 和 ELISA 均发现 MMP-2、MMP-7、MMP-9、TIMP-1 和 TIMP-3 的表达增加。MMPs 和 TIMPs 在 mRNA 和蛋白水平上的表达相互一致。多天之间的事后多重比较分析表明，在病毒感染组中，在 mRNA 和蛋白水平上，在各个 dpi 之间观察到 MMP 和 TIMP 水平显著增加（p < 0.05）。只有在 6 dpi 时 MMP-7 蛋白水平与 5 dpi 相比没有显著差异（p = 0.99）。
结论
在 JEV 感染期间，MMPs 和 TIMPs 的过度表达与中枢神经系统（CNS）疾病的严重程度相关。我们的结果表明，JEV 感染可以改变 CNS 中 MMPs 和 TIMPs 的表达。因此，评估 CNS 感染中的这些重要免疫介质似乎在症状发展中起着重要作用，并有助于了解 JEV 诱导的神经障碍。需要对这个重要的酶学系统进行更多的研究，以研究它们在免疫介导的发病机制中的作用。
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