机构：[1]Department of Ultrasound Diagnosis, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, China[2]Department of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an 710038, China[3]Department of Ultrasound Diagnosis, Xi’an Chest Hospital, Xi’an 710100, China[4]Department of Ultrasound Diagnostics, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China医技科室超声诊断科首都医科大学附属北京同仁医院首都医科大学附属同仁医院
Evidence suggests that various forms of alpha-synuclein- (alpha Syn-) mediated microglial activation are associated with the progression of Parkinson's disease. MicroRNA-155-5p (miR155-5p) is one of the most important microRNAs and enables a robust inflammatory response. Triptolide (T10) is a natural anti-inflammatory component, isolated from a traditional Chinese herb. The objective of the current study was to identify the role and potential regulatory mechanism of T10 in alpha Syn-induced microglial activation via the mi RI55-5p mediated SHIP1 signaling pathway. Mouse primary microglia were exposed to monomers, oligomers, and preformed fibrils (PFFs) of human wild-type aSyn, respectively. The expressions of TNF alpha and IL-1 beta, measured by enzyme-linked immunosorbent assay (ELISA) and qPCR, demonstrated that PFFs initiated the strongest immunogenicity in microglia. Application of inhibitors of tolllike receptor (TLR) 1/2, TLR4, and TLR9 indicated that PFFs activated microglia mainly via the NF-kappa B pathway by binding TLRI/2 and TLR4. Treatment with T10 significantly suppressed PFF-induced microglial activation and attenuated the release of proinflammatory cytokines including TNF alpha and IL-1 beta. Levels of IRAKI, TRAF6, IKK alpha/beta, p-IKK alpha/beta, NF-kappa B, p-NF-kappa B,PI3K, p-PI3K, t-Akt, p-Akt and SHIP1 were measured via Western blot. Levels of miRI55-5p were measured by qPCR. The results demonstrated that SHIP1 acted as a downstream target molecule of miR155-5p. Treatment with T10 did not alter the expression of IRAKI and TRAF6, but significantly decreased the expression of miR155-5p, resulting in upregulation of SHIP1 and repression of NF-kappa B activity, suggesting inhibition of inflammation and microglial activation. The protective effects of T10 were abolished by the use of SHIP1 siRNA and its inhibitor, 3AC, and miR155-5p mimics. In conclusion, our results demonstrated that treatment with T10 suppressed microglial activation and attenuated the release of proinflammatory cytokines by suppressing NF-kappa B activity via targeting the miR155-5p/SH1P1 pathway in PFFs-induced microglial activation.
基金：
National
Natural Science Foundation of China (No. 81671692).
第一作者机构：[1]Department of Ultrasound Diagnosis, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, China[2]Department of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an 710038, China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Feng Yang,Zheng Chuyun,Zhang Yajun,et al.Triptolide Inhibits Preformed Fibril-Induced Microglial Activation by Targeting the MicroRNA155-5p/SHIP1 Pathway[J].OXIDATIVE MEDICINE AND CELLULAR LONGEVITY.2019,2019:doi:10.1155/2019/6527638.
APA：
Feng, Yang,Zheng, Chuyun,Zhang, Yajun,Xing, Changyang,Cai, Wenbin...&Duan, Yunyou.(2019).Triptolide Inhibits Preformed Fibril-Induced Microglial Activation by Targeting the MicroRNA155-5p/SHIP1 Pathway.OXIDATIVE MEDICINE AND CELLULAR LONGEVITY,2019,
MLA：
Feng, Yang,et al."Triptolide Inhibits Preformed Fibril-Induced Microglial Activation by Targeting the MicroRNA155-5p/SHIP1 Pathway".OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2019.(2019)
