DataSheet_1_Oleanolic Acid Acetate Alleviates Symptoms of Experimental Autoimmune Encephalomyelitis in Mice by Regulating Toll-Like Receptor 2 Signaling.docx

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)35-55 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（Toll-like receptor 2, TLR2）表达于中枢神经系统的多种免疫细胞，在神经炎症过程中发挥重要调控作用。已有研究显示，多发性硬化（multiple sclerosis, MS）患者及模拟多发性硬化的实验性自身免疫性脑脊髓炎（experimental autoimmune encephalomyelitis, EAE）小鼠模型体内均存在TLR2表达上调的现象，因此调控TLR2信号通路可成为对抗多发性硬化的有效治疗策略。齐墩果酸乙酸酯（oleanolic acid acetate, OAA）具备抗炎与免疫调节活性，故本研究旨在探讨OAA对EAE模型小鼠体内TLR2信号通路及神经炎症的影响。本研究采用合成的髓鞘少突胶质细胞糖蛋白（myelin oligodendrocyte glycoprotein, MOG）35-55肽诱导C57/BL6小鼠构建EAE模型，并每日给予OAA干预。结果发现，EAE模型小鼠脊髓组织可见后肢瘫痪与炎性细胞浸润现象；其脾脏来源的T细胞增殖水平显著升高；脊髓组织中促炎细胞因子的表达量上调，血清中对应促炎细胞因子的蛋白水平亦有所升高；此外，脊髓组织中TLR2及其下游信号分子的表达均出现上调。经OAA治疗后，上述所有病理改变均得到逆转。本研究结果表明，OAA具有潜在的治疗应用价值，而TLR信号通路可作为多发性硬化的有效治疗靶点。