Institute of Behavior Medicine, 3132 Postle Hall, 305 West 12th Avenue, Ohio State University, Columbus, OH 43210-1094, USA.
Brain Behav Immun. 2011 Jan;25(1):160-7. doi: 10.1016/j.bbi.2010.09.009. Epub 2010 Sep 18.
Interleukin-1 (IL-1) has been implicated in the disease progression of multiple sclerosis (MS). In the animal model of MS, experimental autoimmune encephalomyelitis (EAE), the induction of disease is significantly attenuated in mice lacking the type I IL-1 receptor (IL-1R1). In this study, we created a transgenic mouse (eIL-1R1 kd) in which IL-1R1 expression is knocked down specifically in endothelial cells. Induction of EAE in eIL-1R1 kd mice results in a decrease in incidence, severity and delayed onset of EAE. In addition, eIL-1R1 kd mice show significant decrease in VCAM-1 expression and diminished CD45(+) and CD3(+) infiltrating leukocytes in the spinal cord in animals challenged with EAE. Further, IL-1 and IL-23 stimulate IL-17 production by splenocytes from both wild type and the eIL-1R1 kd animals. Similarly, IL-1 and IL-23 synergistically stimulate splenocytes proliferation in these two strains of animals. After immunization with MOG(79-96), although eIL-1R1 kd mice displayed greatly reduced clinical scores, their splenocytes produced IL-17 and proliferated in response to a second MOG challenge, similar to wild type animals. These findings indicate a critical role for endothelial IL-1R1 in mediating the pathogenesis of EAE, and describe a new model that can be used to study endothelial IL-1R1.
白细胞介素-1（IL-1）与多发性硬化症（MS）的疾病进展有关。在 MS 的动物模型——实验性自身免疫性脑脊髓炎（EAE）中，缺乏 I 型 IL-1 受体（IL-1R1）的小鼠疾病的诱导明显减弱。在这项研究中，我们创建了一种转基因小鼠（eIL-1R1kd），其中内皮细胞特异性敲低了 IL-1R1 的表达。在 eIL-1R1kd 小鼠中诱导 EAE 会导致发病率、严重程度和 EAE 发病时间延迟降低。此外，eIL-1R1kd 小鼠在 EAE 攻击后，脊髓中 VCAM-1 表达和浸润性 CD45（+）和 CD3（+）白细胞明显减少。此外，IL-1 和 IL-23 刺激来自野生型和 eIL-1R1kd 动物的脾细胞产生 IL-17。同样，IL-1 和 IL-23 协同刺激这两种动物的脾细胞增殖。在用 MOG（79-96）免疫后，尽管 eIL-1R1kd 小鼠的临床评分大大降低，但它们的脾细胞在第二次 MOG 挑战时产生了 IL-17 并增殖，与野生型动物相似。这些发现表明内皮细胞 IL-1R1 在介导 EAE 的发病机制中起关键作用，并描述了一种可用于研究内皮细胞 IL-1R1 的新模型。
