Xiong Xiao-Yi, Wang Ting-Gang, Yang Mei-Hua, Meng Zhao-You, Yang Qing-Wu, Wang Fa-Xiang
a Department of Neurology , Xinqiao Hospital, Third Military Medical University , Chongqing , China.
b Department of Emergency Medicine , Southwest Hospital, the Third Military Medical University , Chongqing , China.
Neurol Res. 2016 Feb;38(2):151-7. doi: 10.1080/01616412.2015.1135557.
Interleukin-21 (IL-21) is a cytokine that is an important modulator of immune responses. However, its roles in epilepsy are not completely clear. Here, we investigated the expression and distribution of IL-21 in a kainic acid (KA)-induced acute seizure mouse model.
Mice (n = 146) were randomly divided into an age-matched group, PBS injection group, and a KA injection group. The KA-injected mice were evaluated at 1, 3, and 24 h post-injection. IL-21 mRNA and protein expression levels were measured using RT-PCR and western blotting. Immunohistochemistry and immunofluorescence staining were performed to further characterize the pattern and distribution of IL-21 expression.
The IL-21 mRNA and protein expression levels in the hippocampal tissues of the KA-treated mice were significantly increased as early as 1 h compared with the age-matched mice and PBS-treated mice. After this time point, the expression was reduced, but it remained higher than the level in the PBS-treated mice (p < 0.01). Immunohistochemical staining showed that IL-21 expression was distributed throughout the hippocampus, including areas CA1 and CA3, the dentate gyrus and the hilus. Moreover, immunofluorescence further showed that in the hippocampi of the KA-treated mice, IL-21 was mainly expressed in GFAP-positive astrocytes rather than in NeuN-positive neurons or CD11b-positive microglia.
Our data suggest that an increase in astrocyte-derived IL-21 expression in hippocampal subregions following KA-induced seizures may have potent regulatory effects on epileptogenesis.
白细胞介素-21(IL-21)是一种细胞因子,是免疫反应的重要调节因子。然而,其在癫痫中的作用尚不完全清楚。在此,我们研究了IL-21在 kainic 酸(KA)诱导的急性癫痫发作小鼠模型中的表达和分布。
将小鼠(n = 146)随机分为年龄匹配组、PBS 注射组和 KA 注射组。对注射 KA 的小鼠在注射后1、3和24小时进行评估。使用 RT-PCR 和蛋白质印迹法测量 IL-21 mRNA 和蛋白质表达水平。进行免疫组织化学和免疫荧光染色以进一步表征 IL-21 表达的模式和分布。
与年龄匹配的小鼠和 PBS 处理的小鼠相比,KA 处理的小鼠海马组织中 IL-21 mRNA 和蛋白质表达水平早在1小时就显著增加。在这个时间点之后,表达降低,但仍高于 PBS 处理的小鼠中的水平(p < 0.01)。免疫组织化学染色显示 IL-21 表达分布于整个海马,包括 CA1 和 CA3 区、齿状回和海马门。此外免疫荧光进一步显示,在 KA 处理的小鼠海马中,IL-21 主要表达于 GFAP 阳性星形胶质细胞,而非 NeuN 阳性神经元或 CD11b 阳性小胶质细胞。
我们的数据表明,KA 诱导癫痫发作后海马亚区星形胶质细胞来源的 IL-21 表达增加可能对癫痫发生具有强大调节作用。