Cellular localization and expression patterns of interleukin-10, interleukin-4, and their receptors in multiple sclerosis lesions
Cellular localization and expression patterns of interleukin-10, interleukin-4, and their receptors in multiple sclerosis lesions
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DOI：
10.1002/glia.10050
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发表时间：
2002-04-01
期刊：
影响因子：
6.2
通讯作者：
Van der Valk, P
中科院分区：
文献类型：
--
作者：
Hulshof, S;Montagne, L;Van der Valk, P
细胞因子已被证明在多发性硬化症 (MS) 的发病机制中发挥着至关重要的作用。然而，关于多发性硬化症病变发展过程中中枢神经系统（CNS）内抗炎细胞因子表达的数据仍然有限。因此，我们检测了多发性硬化症患者死后脑组织中抗炎细胞因子白细胞介素 10 (IL-10) 和 IL-4 及其特异性受体 IL-10R 和 IL-4R 的表达。在活动性和慢性多发性硬化症病变中可以观察到两种蛋白质的蛋白质定位和表达的特定模式。在活动性脱髓鞘病变和慢性活动性多发性硬化症病变的超细胞边缘内的反应性星形胶质细胞中观察到最强的 IL-10 免疫反应性。此外，在（慢性）活动性多发性硬化症病变中，血管周围巨噬细胞对 IL-10 呈免疫反应。在慢性活动性和慢性非活动性 MS 病变的细胞减少区域内的反应性纤维星形胶质细胞中检测到最强烈的 IL-4 免疫反应性。在实质和血管周围区域的巨噬细胞以及活动性和慢性 MS 病变中的反应性星形胶质细胞上检测到 IL-10R 和 IL-4R 的强免疫反应性。我们的结果表明 IL-10 和 IL-4 在 CNS 免疫反应中发挥积极作用。 MS 病变不同发展阶段中 IL-10 和 IL-4 的蛋白质定位和蛋白质表达的特定模式表明，这些抗炎细胞因子及其受体参与了导致慢性 MS 病变形成的过程。 (C) 2002 Wiley-Liss, Inc.
Cytokines have been shown to play a crucial role in the pathogenesis of multiple sclerosis (MS). However, still limited data are available on the expression of anti-inflammatory cytokines within the central nervous system (CNS) during MS lesion development. Therefore, we have examined the expression of the anti-inflammatory cytokines, interleukin-10 (IL-10) and IL-4, and their specific receptors, IL-10R and IL-4R, in postmortem human brain tissue obtained from MS patients. Specific patterns of protein localization and expression for both proteins could be observed within active and chronic MS lesions. Strongest IL-10 immunoreactivity was observed in reactive astrocytes within active demyelinating lesions and the hypercellular rim of chronic active MS lesions. Moreover, perivascular macrophages were immunoreactive for IL-10 in (chronic) active MS lesions. Most intense IL-4 immunoreactivity was detected in reactive fibrillary astrocytes within the hypocellular regions of chronic active and chronic inactive MS lesions. Strong immunoreactivity for IL-10R and IL-4R was detected on macrophages in both parenchymal and perivascular areas and on reactive astrocytes in active and chronic MS lesions. Our results indicate that IL-10 and IL-4 have an active role in CNS immune responses. The specific patterns of protein localization and protein expression for both IL-10 and IL-4 in MS lesions at different stages of development suggest that these anti-inflammatory cytokines and their receptors participate in processes leading to the formation of chronic MS lesions. (C) 2002 Wiley-Liss, Inc.