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学科主题: 临床医学
题名:
Hypoxia-Inducible Factor-1 alpha and Interleukin 33 Form a Regulatory Circuit to Perpetuate the Inflammation in Rheumatoid Arthritis
作者: Hu, Fanlei; Shi, Lianjie; Mu, Rong; Zhu, Jiaxin; Li, Yingni; Ma, Xiaoxu; Li, Chun; Jia, Rulin; Yang, Dongyue; Li, Yun; Li, Zhanguo
刊名: PLOS ONE
发表日期: 2013-08-15
DOI: 10.1371/journal.pone.0072650
卷: 8, 期:8
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]: SYNOVIAL FIBROBLASTS ; TNF-ALPHA ; IN-VIVO ; IL-33 ; CYTOKINE ; EXPRESSION ; RECEPTOR ; ST2 ; SYNOVIOCYTES ; CHROMATIN
英文摘要:

Hyperplasia of synovial fibroblasts, infiltration with inflammatory cytokines, and tissue hypoxia are the major characteristics of rheumatoid arthritis (RA). Interleukin 33 (IL-33) is a newly identified inflammatory cytokine exacerbating the disease severity of RA. Hypoxia-inducible factor-1 alpha (HIF-1 alpha) showed increased expression in RA synovium and could regulate a number of inflammatory cytokine productions. Nevertheless, its correlation with IL-33 remains largely unknown. Here, we showed that elevated levels of IL-33 were demonstrated in RA patient synovial fluids, with upregulated expression of HIF-1 alpha and IL-33 in the synovial fibroblasts. Knocking down HIF-1 alpha compromised IL-33 expression in rheumatoid arthritis synovial fibroblasts (RASF), while enforcing HIF-1 alpha expression in RASF substantially upregulated IL-33 levels. HIF-1 alpha promoted the activation of the signalling pathways controlling IL-33 production, particularly the p38 and ERK pathways. Moreover, we showed for the first time that IL-33 in turn could induce more HIF-1 alpha expression in RASF, thus forming a HIF-1 alpha/IL-33 regulatory circuit that would perpetuate the inflammatory process in RA. Targeting this pathological pathway and HIF-1 alpha may provide new therapeutic strategies for overcoming the persistent and chronic inflammatory disease.

语种: 英语
所属项目编号: 2010CB529100 ; 81120108020 ; 81030057 ; 81072401 ; RDB2012-04
项目资助者: 973 program of China ; Natural Science Foundation of China ; Peking University People&prime ; s Hospital Research and Development Funds
WOS记录号: WOS:000323378000109
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64092
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,Shi, Lianjie,Mu, Rong,et al. Hypoxia-Inducible Factor-1 alpha and Interleukin 33 Form a Regulatory Circuit to Perpetuate the Inflammation in Rheumatoid Arthritis[J]. PLOS ONE,2013,8(8).
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