The Interleukin 17 System in Cortical Lesions in Focal Cortical Dysplasias
The Interleukin 17 System in Cortical Lesions in Focal Cortical Dysplasias
复制标题
局灶性皮质发育不良中皮质病变中的白细胞介素 17 系统。
DOI：
10.1097/nen.0b013e318281262e
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发表时间：
2013-02-01
影响因子：
3.2
通讯作者：
Yang, Hui
中科院分区：
文献类型：
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作者：
He, Jiao-Jiang;Li, Song;Yang, Hui
局灶性皮质发育不良（FCD）越来越多地被认为是难治性癫痫的重要原因。为了了解白细胞介素17（IL-17）系统在FCD癫痫发生中的潜在作用，我们研究了15例FCD Ia型（FCDIa）、12例FCD IIa型（FCDIIa）和12例FCD IIb型（FCDIIb）皮质病变中IL-17系统的表达模式，并将结果与10例对照患者的大脑皮质进行比较。在FCDIa、FCDIIa和FCDIIb中，IL-17、IL-17受体（IL-17 R）和IL-17通路下游因子（核因子-κB激活因子1 [NFκB; ACT 1]和NFκB-p65）的蛋白水平显著升高。此外，IL-17和IL-17 R蛋白水平与FCD患者的癫痫发作频率呈正相关。免疫组化结果显示，IL-17和IL-17 R在神经元微柱、畸形神经元、球囊细胞、星形胶质细胞和血管内皮细胞中高度表达。NF-κB B活化因子1和NF-κB-p65在FCD中呈弥漫性表达。此外，我们在FCDIIa和FCDIIb中检测到少量IL-17阳性、CD 4阳性T淋巴细胞，但在FCDIa中未检测到。总之，这些发现表明，IL-17系统的过表达和IL-17信号转导通路的激活可能参与FCD中皮质病变的致痫性，因此代表了抗癫痫治疗的新的潜在靶点。
Focal cortical dysplasias (FCDs) are increasingly recognized as important causes of medically intractable epilepsy. To understand the potential role of the interleukin 17 (IL-17) system in the epileptogenesis of FCDs, we studied the expression patterns of the IL-17 system in 15 FCD type Ia (FCDIa), 12 FCD type IIa (FCDIIa), and 12 FCD type IIb (FCDIIb) cortical lesions and compared the results with those in cerebral cortex from 10 control patients. Protein levels of IL-17, IL-17 receptor (IL-17R), and downstream factors of the IL-17 pathway (nuclear factor-κB activator 1 [NFκB; ACT1] and NFκB-p65) were markedly elevated in FCDIa, FCDIIa, and FCDIIb. Moreover, protein levels of IL-17 and IL-17R positively correlated with the frequency of seizures in FCD patients. Immunostaining indicated that IL-17 and IL-17R are highly expressed in neuronal microcolumns, dysmorphic neurons, balloon cells, astrocytes, and vascular endothelial cells. Nuclear factor-κB activator 1 and NFκB-p65 were diffusely expressed in FCDs. In addition, we detected a few IL-17-positive, CD4-positive T lymphocytes in FCDIIa and FCDIIb but not in FCDIa. Taken together, these findings suggest that the overexpression of the IL-17 system and the activation of the IL-17 signal transduction pathway may be involved in the epileptogenicity of cortical lesions in FCDs, thus representing a novel potential target for antiepileptic therapy.