Wang Yan, Zhao Jingxia, Di Tingting, Wang Mingxing, Ruan Zhitong, Zhang Lu, Xie Xiangjiang, Meng Yujiao, Lin Yan, Liu Xin, Wang Ning, Li Ping
Beijing Hospital of Traditional Chinese Medicine, affiliated with Capital Medical University, Beijing 100010, China; Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China.
Beijing Hospital of Traditional Chinese Medicine, affiliated with Capital Medical University, Beijing 100010, China; Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China.
Int Immunopharmacol. 2016 Nov;40:410-418. doi: 10.1016/j.intimp.2016.09.029. Epub 2016 Sep 30.
β,β-dimethylacryloyl alkannin (DMA) is a key component of Lithospermum and possesses good efficacy for treating psoriasis. DMA inhibits activated dendritic cells (DCs), but the mechanism is unknown. Therefore, this study aimed to explore the modulation of the TLR7/8 pathway by DMA in psoriasis-activated DCs. Models of psoriasis-like skin lesions were established using BALB/c mice; 8 mice were treated with DMA (2.5mg/kg). Bone marrow cells were isolated and induced into DCs using R848, a TLR7/8 agonist. Splenic CD11c+ cells were detected by flow cytometry. Skin CD11c+ cells were detected by immunofluorescence. TLR7, TLR8, MYD88, and IRAKM proteins were detected by Western blot. The effects of DMA on surface molecules of DCs were observed by flow cytometry. mRNA expression of inflammatory factors was detected by qRT-PCR. Secreted cytokines were detected by cytometric bead array. Compared with the model group, psoriasis-like skin lesions were alleviated by DMA, the splenic CD11c+ cells were significantly decreased (P<0.01), and CD11c+ cell numbers in skin lesions were decreased (P<0.01). Expression levels of TLR7, MYD88, and IRAKM were significantly decreased (P<0.05). R848-stimulated DCs showed increased expression of I-A/I-E, CD80, and CD86 (P<0.01), increased IL-23 and IL-1β mRNA and secretion (P<0.05), and increased TLR7, TLR8, MYD88, and IRAKM expression (P<0.01); DMA inhibited all of these effects of the TLR7/8 pathway activation by R848 (P<0.05). In conclusion, DMA could inhibit psoriasis-activated DCs via the TLR7/8 pathway.
β,β-二甲基丙烯酰紫草素（DMA）是紫草的关键成分，对治疗银屑病具有良好疗效。DMA可抑制活化的树突状细胞（DCs），但其机制尚不清楚。因此，本研究旨在探讨DMA对银屑病活化DCs中TLR7/8通路的调节作用。采用BALB/c小鼠建立银屑病样皮肤损伤模型；8只小鼠用DMA（2.5mg/kg）治疗。分离骨髓细胞，并用TLR7/8激动剂R848诱导为DCs。通过流式细胞术检测脾CD11c+细胞。通过免疫荧光检测皮肤CD11c+细胞。通过蛋白质印迹法检测TLR7、TLR8、MYD88和IRAKM蛋白。通过流式细胞术观察DMA对DCs表面分子的影响。通过qRT-PCR检测炎性因子的mRNA表达。通过细胞因子珠阵列检测分泌的细胞因子。与模型组相比，DMA可减轻银屑病样皮肤损伤，脾CD11c+细胞显著减少（P<0.01），皮肤损伤中CD11c+细胞数量减少（P<0.01）。TLR7、MYD88和IRAKM的表达水平显著降低（P<0.05）。R848刺激的DCs显示I-A/I-E、CD80和CD86表达增加（P<0.01），IL-23和IL-1β mRNA及分泌增加（P<0.05），TLR7、TLR8、MYD88和IRAKM表达增加（P<0.01）；DMA抑制了R848激活TLR7/8通路的所有这些作用（P<0.05）。综上所述，DMA可通过TLR7/8通路抑制银屑病活化的DCs。
