Interferon-γ-oligodendrocyte interactions in the regulation of experimental autoimmune encephalomyelitis
Interferon-γ-oligodendrocyte interactions in the regulation of experimental autoimmune encephalomyelitis
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DOI：
10.1523/jneurosci.4689-06.2007
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发表时间：
2007-02-21
影响因子：
5.3
通讯作者：
Popko, Brian
中科院分区：
文献类型：
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作者：
Balabanov, Roumen;Strand, Krystle;Popko, Brian
实验性自身免疫性脑脊髓炎（EAE）是人类脱髓鞘疾病多发性硬化症（MS）的动物模型。免疫细胞因子干扰素-γ（IFN-γ）被认为是参与疾病的发病机制，在EAE和MS。在本研究中，我们研究了IFN-γ-少突胶质细胞的相互作用在EAE的过程中的意义。为了我们研究的目的，我们使用了先前描述的[蛋白脂质蛋白/细胞因子信号转导抑制因子1（PLP/SOCS 1）]转基因小鼠系，该转基因小鼠系显示出对IFN-γ的抑制的少突胶质细胞反应性。PLP/SOCS 1小鼠发生EAE，其加速发作与增强的早期炎症和显著增加的少突胶质细胞凋亡相关。此外，我们发现，IFN-γ预处理的成熟少突胶质细胞在体外具有抗氧化应激和抑制蛋白酶体活性的保护作用，并导致上调的表达的一些趋化因子，包括CXCL 10（IP 10），CCL 2（MCP-1），CCL 3（MCP-1 α），和CCL 5（RANTES）。这些结果表明，IFN-γ-少突胶质细胞的相互作用是EAE的临床和病理方面的意义。此外，本研究表明，少突胶质细胞不是简单的炎症损伤的目标，但在EAE过程中的神经免疫网络的积极参与者。
Experimental autoimmune encephalomyelitis ( EAE) is an animal model of the human demyelinating disorder multiple sclerosis ( MS). The immune cytokine interferon- gamma ( IFN-gamma) is believed to participate in disease pathogenesis in both EAE and MS. In the present study, we examined the significance of IFN-gamma - oligodendrocyte interactions in the course of EAE. For the purpose of our study, we used the previously described [proteolipid protein/ suppressor of cytokine signaling 1 (PLP/SOCS1)] transgenic mouse line that displays suppressed oligodendrocyte responsiveness to IFN-gamma. PLP/SOCS1 mice developed EAE with an accelerated onset associated with enhanced early inflammation and markedly increased oligodendrocyte apoptosis. Moreover, we found that IFN-gamma pretreatment of mature oligodendrocytes in vitro had a protective effect against oxidative stress and the inhibition of proteasome activity and resulted in upregulation in expression of a number of chemokines, including CXCL10 ( IP10), CCL2 ( MCP-1), CCL3 ( MCP-1 alpha), and CCL5 ( RANTES). These results suggest that IFN-gamma- oligodendrocyte interactions are of significance to the clinical and pathological aspects of EAE. In addition, the present study suggests that oligodendrocytes are not simply targets of inflammatory injury but active participants of the neuroimmune network operating during the course of EAE.