期刊
FRONTIERS IN IMMUNOLOGY
卷 11, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2020.556526
关键词
leonurine; Treg Th17; rheumatoid arthritis; TAZ; balance
类别
资金
- Natural Science Foundation of Guangdong Province [2019A1515011636]
- Guangzhou Science and Technology Bureau [201904010177]
- First Affiliated Hospital of Guangzhou University of Chinese Medicine [2019QN08]
- Guangdong Administration of Traditional Chinese Medicine [20191110]
- Medical research fund project of Guangdong Province [A2020409]
Leonurine, an active alkaloid extracted fromHerba leonuri, is reported to have potent anti-inflammatory activity against rheumatoid arthritis (RA). However, the molecular mechanism of action of leonurine in RA remains poorly understood. In this study, we detected 3,425 mRNAs differentially expressed between CD4(+)T cells of RA patients and those of healthy individuals using microarray raw data mining. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that transcriptional coactivator with PDZ-binding motif (TAZ) regulates a variety of biological processes including T-helper (Th)-17 cell development, and was thus selected for functional verification. In a naive CD4(+)T cell differentiation assay, we found that TAZ overexpression was associated with impaired balance between T regulatory (Treg) and Th17 cellsin vitro. TAZ overexpression increased the levels of the pro-inflammatory cytokines interleukin (IL)-17, IL-1 beta, and tumor necrosis factor (TNF)-alpha and decreased that of the anti-inflammatory cytokine IL-10. Leonurine treatment had a direct recovery effect on the impaired balance and reduced the expression of TAZ and led to normalization of IL-17, IL-1 beta, and TNF-alpha and IL-10. Furthermore, IL-6 was found to promote the expression of TAZ and receptor activator of nuclear factor kappa-B ligand (RANKL), and RANK. Leonurine significantly inhibited TAZ-mediated expression of RANKL, and RANK and IL-6 in synovial fibroblasts. We conclude that the therapeutic effect of leonurine was through suppression of TAZ led to restoration of Treg/Th17 balance and suppression of synovial fibroblast action.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据