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学科主题: 临床医学
题名:
Toll-Like Receptors Expressed by Synovial Fibroblasts Perpetuate Th1 and Th17 Cell Responses in Rheumatoid Arthritis
作者: Hu, Fanlei; Li, Yingni; Zheng, Li; Shi, Lianjie; Liu, Hongjiang; Zhang, Xuewu; Zhu, Huaqun; Tang, Sumei; Zhu, Lei; Xu, Liling; Yang, Yuqin; Li, Zhanguo
刊名: PLOS ONE
发表日期: 2014-06-17
DOI: 10.1371/journal.pone.0100266
卷: 9, 期:6
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: TISSUE ; SYNOVIOCYTES ; BLOCKADE ; DISEASES ; HYPOXIA ; ALPHA ; FLUID ; VIVO ; DNA
英文摘要:

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial fibroblast hyperplasia and bone and cartilage erosion. Synovial fibroblast- and T cell-mediated inflammation plays crucial roles in the pathogenesis of RA. However how this inflammation is initiated, propagated, and maintained remains controversial. Here, we systemically examined the contribution of toll-like receptors (TLRs) to the inflammatory mediator production as well as Th1 and Th17 cell hyperactivity in RA. Our results show that rheumatoid arthritis synovial fibroblasts (RASF) express a series of TLRs, including TLR2, TLR3, TLR4, and TLR9, with the predominant expression of TLR3. Moreover, the expression levels of these TLRs were higher than those in osteoarthritis synovial fibroblasts (OASF). Ligation of TLR3, as well as TLR2 and TLR4, resulted in vigorous production of inflammatory cytokines, matrix metalloproteinases (MMPs), and vascular endothelial growth factor (VEGF) in RASF, with activation of the NF-kappa B, MAPK, and IRF3 pathways. More important, activation of these TLRs expressed by RASF exacerbated inflammatory Th1 and Th17 cell expansion both in cell-cell contact-dependent and inflammatory cytokine-dependent manners, which induced more IFN-gamma and IL-17 accumulation. Targeting TLRs may modulate the inflammation in RA and provide new therapeutic strategies for overcoming this persistent disease.

语种: 英语
所属项目编号: 81302554 ; 81030057 ; 2010CB529100 ; RDB2012-04 ; RDB2013-04
项目资助者: Natural Science Foundation of China ; 973 program of China ; Peking University People&prime ; s Hospital
WOS记录号: WOS:000338503400099
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62084
Appears in Collections:北京大学第二临床医学院_期刊论文

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作者单位: Peking Univ, Peoples Hosp, Dept Rheumatol & Immunol, Beijing 100871, Peoples R China

Recommended Citation:
Hu, Fanlei,Li, Yingni,Zheng, Li,et al. Toll-Like Receptors Expressed by Synovial Fibroblasts Perpetuate Th1 and Th17 Cell Responses in Rheumatoid Arthritis[J]. PLOS ONE,2014,9(6).
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