Kim Minju, Lee Soyoung, Lim Hyungjin, Lee Jihye, Park Ji-Young, Kwon Hyung-Jun, Lee In-Chul, Ryu Young-Bae, Kim Jeongtae, Shin Taekyun, Ahn Ginnae, Rho Mun-Chual, Jung Kyungsook
Department of Marine Bio-Food Sciences, Chonnam National University, Yeosu, South Korea.
Immunoregulatory Materials Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup-si, South Korea.
Front Pharmacol. 2020 Sep 3;11:556391. doi: 10.3389/fphar.2020.556391. eCollection 2020.
Toll-like receptor 2 (TLR2) is expressed by several immune cells in the central nervous system and plays an important role in neuroinflammation. TLR2 upregulation has been reported in multiple sclerosis patients and in experimental autoimmune encephalomyelitis (EAE), a mouse model for multiple sclerosis. Therefore, modulating TLR2 signaling can be an effective treatment strategy against MS. Oleanolic acid acetate (OAA) has antiinflammatory and immunomodulatory effects. Hence, this study aimed to examine the effects of OAA on TLR2 signaling and neuroinflammation in EAE. EAE was induced in C57/BL6 mice using synthesized myelin oligodendrocyte glycoprotein (MOG) peptide, and OAA was administered daily. Hind limb paralysis and inflammatory cell infiltration were observed in the spinal cords of EAE mice. Moreover, T-cell proliferation was significantly stimulated in splenic cells from EAE mice. The expression of proinflammatory cytokines in the spinal cord was upregulated, and their serum protein levels were increased in EAE mice. Furthermore, upregulation of TLR2 and downstream signaling molecules was observed in the spinal cord. These pathological changes were reversed by OAA treatment. Our results suggest that OAA might have promising therapeutic properties and that the TLR signaling pathway is an effective therapeutic target against multiple sclerosis.
Toll样受体2（TLR2）在中枢神经系统的多种免疫细胞中表达，并在神经炎症中起重要作用。在多发性硬化症患者和实验性自身免疫性脑脊髓炎（EAE，一种多发性硬化症的小鼠模型）中，已报道有TLR2上调。因此，调节TLR2信号传导可能是一种针对MS的有效治疗策略。齐墩果酸醋酸酯（OAA）具有抗炎和免疫调节作用。因此，本研究旨在研究OAA对EAE中TLR2信号传导和神经炎症的影响。使用合成的髓鞘少突胶质细胞糖蛋白（MOG）肽在C57/BL6小鼠中诱导EAE，并每日给予OAA。在EAE小鼠的脊髓中观察到后肢麻痹和炎性细胞浸润。此外，EAE小鼠脾细胞中的T细胞增殖受到显著刺激。EAE小鼠脊髓中促炎细胞因子的表达上调，其血清蛋白水平升高。此外，在脊髓中观察到TLR2和下游信号分子的上调。这些病理变化通过OAA治疗得到逆转。我们的结果表明，OAA可能具有良好的治疗特性，并且TLR信号通路是针对多发性硬化症的有效治疗靶点。
