Kobayashi Kunitoshi, Tomiki Hiroki, Inaba Yuji, Ichikawa Motoki, Kim Byung S, Koh Chang-Sung
Department of Biomedical Laboratory Sciences, Graduate School of Medicine, Matsumoto, Nagano 390-8621, Japan.
Department of Pediatrics, School of Medicine, Shinshu University, Matsumoto, Nagano 390-8621, Japan.
Int Immunol. 2015 Jul;27(7):333-44. doi: 10.1093/intimm/dxv006. Epub 2015 Feb 26.
Dimethyl fumarate (DMF) is a modifier of the nuclear factor (erythroid-derived 2)-2 (Nrf2)-kelch-like ECH-associated protein 1 (Keap1) pathway. DMF treatment in the effector phase significantly suppressed the development of Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) both clinically and histologically. DMF treatment leads to an enhanced Nrf2 antioxidant response in TMEV-IDD mice. DMF treatment in the effector phase significantly suppressed the level of IL-17A mRNA. DMF is known to inhibit differentiation of T helper 17 (Th17) cells via suppressing NF-κB. Taken together, our data suggest that DMF treatment in the effector phase may suppress TMEV-IDD not only via enhancing the antioxidant response but also via suppressing IL-17A.
富马酸二甲酯（DMF）是核因子（红系衍生2）-2（Nrf2）- Kelch样ECH相关蛋白1（Keap1）信号通路的调节剂。在效应期进行DMF治疗，在临床和组织学上均显著抑制了泰勒氏鼠脑脊髓炎病毒诱导的脱髓鞘疾病（TMEV-IDD）的发展。DMF治疗可增强TMEV-IDD小鼠的Nrf2抗氧化反应。在效应期进行DMF治疗可显著抑制IL-17A mRNA的水平。已知DMF通过抑制核因子κB（NF-κB）来抑制辅助性T细胞17（Th17）细胞的分化。综上所述，我们的数据表明，在效应期进行DMF治疗可能不仅通过增强抗氧化反应，还通过抑制IL-17A来抑制TMEV-IDD。
