Multiple sclerosis (MS), an immune-mediated and neurodegenerative disorder of the central nervous system (CNS), is characterized by infiltrating myelin-reactive T lymphocytes and demyelinating lesions. Experimental autoimmune encephalomyelitis (EAE) is a well-established animal model used to study MS. To explore the impact of chemokine receptor CCR1 blockade in EAE and the underlying mechanisms, we used CCR1 antagonist J-113863 in PLP_139-151-induced EAE in SJL/J mice. Following EAE induction, mice were treated with J-113863 (10 mg/kg) daily from day 14 until day 25. We investigated the effect of J-113863 on expression levels of GM-CSF, IL-6, IL-10, IL-27 in CD4⁺ spleen cells, using flow cytometry. We also analyzed the effect of J-113863 on GM-CSF, IL-6, IL-10, IL-27 mRNA and protein expression levels using RT-PCR and Western blot analysis in brain tissues. J-113863 treatment decreased the populations of CD4⁺GM-CSF⁺ and CD4⁺IL-6⁺ cells and increased CD4⁺IL-27⁺ and CD4⁺IL-10⁺ cells in the spleen. J-113863 had a suppressive effect on the mRNA and protein expression levels of GM-CSF, and IL-6 in the brain tissue. On the other hand, J-113863 treatment increased the mRNA and protein expression of IL-10 and IL-27 in the brain tissue. Our results highlighted J-113863′s potential role in suppressing pro-inflammatory expression and up-regulating anti-inflammatory mediators, which could represent a beneficial alternative approach to MS treatment.

多发性硬化症 (MS) 是一种免疫介导的中枢神经系统 (CNS) 神经退行性疾病，其特征是浸润髓鞘反应性 T 淋巴细胞和脱髓鞘病变。实验性自身免疫性脑脊髓炎 (EAE) 是一种成熟的用于研究 MS 的动物模型。为了探索趋化因子受体 CCR1 阻断在 EAE 中的影响及其潜在机制，我们在 SJL/J 小鼠的 PLP _{139-151诱导的 EAE 中使用了 CCR1 拮抗剂 J-113863。}在 EAE 诱导后，从第 14 天到第 25 天，每天用 J-113863 (10 mg/kg) 治疗小鼠。我们研究了 J-113863 对 GM-CSF、IL-6、IL-10、IL 表达水平的影响-27 在 CD4 ⁺脾细胞，使用流式细胞仪。我们还使用 RT-PCR 和蛋白质印迹分析在脑组织中分析了 J-113863 对 GM-CSF、IL-6、IL-10、IL-27 mRNA 和蛋白质表达水平的影响。J-113863 处理减少了 CD4 ⁺ GM-CSF ⁺和 CD4 ⁺ IL-6 ⁺细胞的数量并增加了 CD4 ⁺ IL-27 ⁺和 CD4 ⁺ IL-10 ⁺脾脏中的细胞。J-113863 对脑组织中 GM-CSF 和 IL-6 的 mRNA 和蛋白质表达水平具有抑制作用。另一方面，J-113863 治疗增加了脑组织中 IL-10 和 IL-27 的 mRNA 和蛋白质表达。我们的研究结果强调了 J-113863 在抑制促炎表达和上调抗炎介质方面的潜在作用，这可能代表了一种有益的 MS 治疗替代方法。