CXC chemokine receptors on human oligodendrocytes: implications for multiple sclerosis
CXC chemokine receptors on human oligodendrocytes: implications for multiple sclerosis
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DOI：
10.1093/brain/awh479
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发表时间：
2005-05-01
期刊：
影响因子：
14.5
通讯作者：
Raine, CS
中科院分区：
文献类型：
--
作者：
Omari, KM;John, GR;Raine, CS
在多发性硬化症脱髓鞘后，髓鞘修复发生，但随着病变的年龄，髓鞘再生的能力减弱。中枢神经系统髓鞘再生过程中少突胶质细胞行为的分子途径仍有待阐明。在这项研究中，我们报告的第一次组成型表达的CXC/α趋化因子受体，CXCR 1，CXCR 2和CXCR 3，少突胶质细胞在正常成人中枢神经系统组织，其水平上调多发性硬化症和其他神经系统疾病（OND）。此外，体外培养的未成熟（A2 B5（+）/O 4（+））和更成熟（CN（+））的人少突胶质细胞表达相同的三种受体。CXCR 1、CXCR 2和CXCR 3的相应配体[即CXCL 8/IL-8、CXCL 1/GRO-α和CXCL 10/IP-10]在正常人和OND受试者的CNS组织中不存在，但在活动性（但非沉默性）多发性硬化病变边缘的肥大（反应性）星形胶质细胞上以高水平存在。体外培养的星形胶质细胞经促炎细胞因子刺激后可诱导表达趋化因子。人星形胶质细胞在RNA和蛋白质水平上产生CXCL 8和CXCL 1可由白细胞介素（IL）-1 β诱导，而CXCL 10可由IL-1 β和干扰素-γ诱导。由于这些细胞因子是在活动性多发性硬化病变边缘发生的炎性事件的组成部分，它们在这些区域中的上调可能是本文观察到的趋化因子表达动态的基础。同时表达不同的CXC趋化因子受体的少突胶质细胞，和他们的配体对周围的多发性硬化症病变的星形胶质细胞，可能预示着新的功能作用，这些免疫系统分子的招募少突胶质细胞和髓鞘再生。
Subsequent to demyelination in multiple sclerosis, myelin repair occurs but, as lesions age, the ability to remyelinate diminishes. Molecular pathways underlying oligodendrocyte behaviour during CNS remyelination remain to be elucidated. In this study, we report for the first time constitutive expression of the CXC/alpha chemokine receptors, CXCR1, CXCR2 and CXCR3, on oligodendrocytes in normal adult human CNS tissue, the levels of which were upregulated in multiple sclerosis and other neurological diseases (OND). In addition, both immature (A2B5(+)/O4(+)) and more mature (CNPase(+)) human oligodendrocytes in vitro expressed the same three receptors. The respective ligands to CXCR1, CXCR2 and CXCR3 [i.e. CXCL8/IL-8, CXCL1/GRO-alpha and CXCL10/IP-10), were absent in CNS tissue from normals and subjects with OND, but were present at high levels on hypertrophic (reactive) astrocytes at the edge of active (but not silent) multiple sclerosis lesions. Astrocytes in vitro could be induced to express chemokines following stimulation with pro-inflammatory cytokines. CXCL8 and CXCL1 production by human astrocytes at both the RNA and protein levels could be induced by interleukin (IL)-1 beta, while CXCL10 was induced by both IL-1 beta and interferon-gamma. Since these cytokines are integral to inflammatory events occurring at the margins of active multiple sclerosis lesions, their upregulation in these regions may underlie the dynamics of chemokine expression observed herein. The simultaneous expression of different CXC chemokine receptors on oligodendrocytes, and their ligands on astrocytes around multiple sclerosis lesions, may bespeak novel functional roles for these immune system molecules in the recruitment of oligodendrocytes and remyelination.