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学科主题: 临床医学
题名:
High mobility group box 1 contributes to anti-neutrophil cytoplasmic antibody-induced neutrophils activation through receptor for advanced glycation end products (RAGE) and Toll-like receptor 4
作者: Wang, Chen; Wang, Huan; Chang, Dong-Yuan; Hao, Jian; Zhao, Ming-Hui; Chen, Min1
刊名: ARTHRITIS RESEARCH & THERAPY
发表日期: 2015-03-18
DOI: 10.1186/s13075-015-0587-4
卷: 17
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Rheumatology
研究领域[WOS]: Rheumatology
关键词[WOS]: ANCA-ASSOCIATED VASCULITIS ; ANTIMYELOPEROXIDASE ANTIBODIES ; SIGNAL-TRANSDUCTION ; CHROMATIN PROTEIN ; MOLECULAR-PATTERN ; IMMUNE-RESPONSES ; SERUM HMGB1 ; INFLAMMATION ; INDUCTION ; PATHWAYS
英文摘要:

Introduction: High mobility group box-1 (HMGB1), a typical damage-associated molecular pattern (DAMP) protein, is associated with inflammatory conditions and tissue damage. Our recent study found that circulating HMGB1 levels could reflect the disease activity of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The current study aimed to investigate whether HMGB1 participated in ANCA-induced neutrophil activation, which is one of the most important pathogenic aspects in the development of AAV.

Methods: The various effects of HMGB1 in ANCA-induced neutrophil activation were measured. Antagonists for relevant receptors and signaling molecules were employed.

Results: ANCA antigens translocation on neutrophils primed with HMGB1 was significantly higher than non-primed neutrophils. The levels of respiratory burst and degranulation increased significantly in HMGB1-primed neutrophils activated with ANCA-positive IgG, as compared with non-primed neutrophils. Furthermore, blocking Toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE), rather than TLR2, resulted in a significant decrease in HMGB1-induced ANCA antigens translocation, respiratory burst and degranulation. Similar effects were also found when blocking MyD88 and NF-kappa B.

Conclusions: HMGB1 could prime neutrophils by increasing ANCA antigens translocation, and the primed neutrophils could be further induced by ANCA, resulting in the respiratory burst and degranulation. This process is TLR4- and RAGE-dependent through the MyD88/NF-kappa B pathway.

语种: 英语
所属项目编号: 2012CB517702 ; 81425008 ; 81321064 ; 81300599 ; 2011BAI10B04
项目资助者: Chinese 973 project ; National Natural Science Fund ; &prime ; National Key Technology Research and Development (R&amp ; D) Program&prime ; of the Ministry of Science and Technology of China
WOS记录号: WOS:000352136600001
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/66335
Appears in Collections:北京大学第一临床医学院_肾脏内科_期刊论文

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作者单位: 1.Peking Univ, Hosp 1, Dept Med, Div Renal, Beijing 100034, Peoples R China
2.Peking Univ, Inst Nephrol, Minist Hlth China, Key Lab Renal Dis, Beijing 100034, Peoples R China

Recommended Citation:
Wang, Chen,Wang, Huan,Chang, Dong-Yuan,et al. High mobility group box 1 contributes to anti-neutrophil cytoplasmic antibody-induced neutrophils activation through receptor for advanced glycation end products (RAGE) and Toll-like receptor 4[J]. ARTHRITIS RESEARCH & THERAPY,2015,17.
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