Differential expression of metallothioneins in the CNS of mice with experimental autoimmune encephalomyelitis
Differential expression of metallothioneins in the CNS of mice with experimental autoimmune encephalomyelitis
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DOI：
10.1016/s0306-4522(01)00252-4
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发表时间：
2001-01-01
期刊：
影响因子：
3.3
通讯作者：
Martínez-Cáceres, EM
中科院分区：
文献类型：
--
作者：
Espejo, C;Carrasco, J;Martínez-Cáceres, EM
多发性硬化症是一种中枢神经系统的炎性脱髓鞘疾病。金属硫蛋白-I +II是由固定应激、创伤或退行性疾病在CNS中诱导的抗氧化蛋白质，其被假定发挥神经保护作用，而CNS同种型金属硫蛋白-III与阿尔茨海默病相关。我们分析了金属硫蛋白-I-III在实验性自身免疫性脑脊髓炎小鼠中枢神经系统中的表达。此外，我们还研究了在具有两种不同遗传背景的干扰素-γ受体敲除小鼠的实验性自身免疫性脑脊髓炎期间，干扰素-γ（一种促炎细胞因子）在控制金属硫蛋白表达中的假定作用：129/Sv和C57 BL/6 × 129/Sv。患有实验性自身免疫性脑脊髓炎的小鼠在脊髓白色物质中显示出金属硫蛋白-I +II的显著诱导，在大脑中的程度较低。干扰素-γ受体敲除小鼠患有更严重的实验性自身免疫性脑脊髓炎，有趣的是，在脊髓和大脑的白色和灰质中均显示出更高的金属硫蛋白-I +II诱导。与金属硫蛋白-I +II亚型相反，金属硫蛋白-III表达在实验性自身免疫性脑脊髓炎期间基本保持不变;干扰素-γ受体敲除小鼠仅在C57 BL/6x 129/Sv背景中显示改变的金属硫蛋白-III表达（脊髓白色物质轻微增加）。金属硫蛋白-I +II蛋白在诱导细胞浸润的区域中突出。反应性星形胶质细胞和活化的单核细胞/巨噬细胞是金属硫蛋白-I +II蛋白的来源。从这些结果我们认为，金属硫蛋白-I +II，而不是金属硫蛋白-III可能在实验性自身免疫性脑脊髓炎中发挥重要作用，并表明促炎细胞因子干扰素-γ是不太可能在这种反应的重要因素。(C)2001年IBRO。由爱思唯尔科技有限公司出版。保留所有权利。
Multiple sclerosis is an inflammatory, demyelinating disease of the CNS. Metallothioneins-I+II are antioxidant proteins induced in the CNS by immobilisation stress, trauma or degenerative diseases which have been postulated to play a neuroprotective role, while the CNS isoform metallothionein-III has been related to Alzheimer's disease. We have analysed metallothioneins-I-III expression in the CNS of mice with experimental autoimmune encephalomyelitis. Moreover, we have examined the putative role of interferon-gamma, a pro-inflarnmatory cytokine, in the control of metallothioneins expression during experimental autoimmune encephalomyelitis in interferon-gamma receptor knockout mice with two different genetic backgrounds: 129/Sv and C57BL/6x129/Sv.Mice with experimental autoimmune encephalomyelitis showed a significant induction of metallothioneins-I+II in the spinal cord white matter, and to a lower extent in the brain. Interferon-gamma receptor knockout mice suffered from a more severe experimental autoimmune encephalomyelitis, and interestingly showed a higher metallothioneins-I+II induction in both white and grey matter of the spinal cord and in the brain. In contrast to the metallothioneins-I+II isoforms, metallothionein-III expression remained essentially unaltered during experimental autoimmune encephalomyelitis; interferon-gamma receptor knockout mice showed an altered metallothionein-III expression (a slight increase in the spinal cord white matter) only in the C57BL/6x129/Sv background. Metallothioneins-I+II proteins were prominent in areas of induced cellular infiltrates. Reactive astrocytes and activated monocytes/macrophages were the sources of metallothioneins-I+II proteins.From these results we suggest that metallothioneins-I+II but not metallothionein-III may play an important role during experimental autoimmune encephalomyelitis, and indicate that the pro-inflammatory cytokine interferon-gamma is unlikely an important factor in this response. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.