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学科主题: 临床医学
题名:
Human Secreted Stabilin-1-Interacting Chitinase-like Protein Aggravates the Inflammation Associated With Rheumatoid Arthritis and Is a Potential Macrophage Inflammatory Regulator in Rodents
作者: Xiao, Weichun1; Meng, Geng1; Zhao, Yanmei1; Yuan, Huihui2; Li, Tingting1; Peng, Yanyan1; Zhao, Yong3; Luo, Ming4; Zhao, Wenming2; Li, Zhanguo5; Zheng, Xiaofeng1
刊名: ARTHRITIS & RHEUMATOLOGY
发表日期: 2014-05-01
DOI: 10.1002/art.38356
卷: 66, 期:5, 页:1141-1152
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]: COLLAGEN-INDUCED ARTHRITIS ; COLONY-STIMULATING FACTOR ; SI-CLP ; ALTERNATIVE ACTIVATION ; CYTOKINE PRODUCTION ; CELLS ; EXPRESSION ; MODEL ; MICE ; DIFFERENTIATION
英文摘要:

Objective. To study the relationship between the human secreted protein stabilin-1-interacting chitinase-like protein (SI-CLP) and rheumatoid arthritis (RA).

Methods. The expression of SI-CLP in peripheral blood mononuclear cells (PBMCs) and synovial fluid from patients with RA and the effects of cytokines on SI-CLP expression were examined by Western blotting. Fluorescence-activated cell sorting analysis was performed to investigate the binding between SI-CLP and cells. Bone marrow-derived macrophages were isolated from wild-type and SI-CLP-/- mice, and real-time quantitative polymerase chain reaction was performed to detect the levels of messenger RNA for cytokines or SI-CLP in SI-CLP- or cytokine-treated macrophages. Histologic studies were conducted to evaluate inflamma-tion and the expression of interleukin-12 (IL-12), IL-13, and SI-CLP in lesions. Enzyme-linked immunosorbent assays were used to detect the cytokine levels in bone marrow-derived macrophages. Rats or mice with collagen-induced arthritis (CIA) and SI-CLP-/- mice were used to study the function of SI-CLP in RA.

Results. SI-CLP expression was increased in PBMCs and detectable in synovial fluid from patients with RA. Administration of SI-CLP to rats with CIA aggravated arthritis-associated inflammation. SI-CLP was specifically attached to the surface protein of macrophages, which elevated the expression of IL-1 beta, IL-6, IL-12, and IL-13 in macrophages and mouse bone marrow-derived macrophages, up-regulating ERK phosphorylation. Moreover, SI-CLP was up-regulated by both IL-12 and IL-13 through JNK and JAK/STAT signaling, respectively. Knockout of SI-CLP resulted in a decrease in the expression of IL-1 beta, IL-6, IL-12, and IL-13 and lower susceptibility to CIA compared with wild-type mice. SI-CLP treatment also aggravated arthritis-related inflammation in wild-type and SI-CLP-/- mice.

Conclusion. SI-CLP functions as a regulator of the inflammatory response by macrophages. The decrease in inflammation-associated cytokine levels resulting from SI-CLP knockout may explain the lower susceptibility to CIA in SI-CLP-/- mice.

语种: 英语
所属项目编号: 2010CB911800 ; 2010CB529106 ; 30930020 ; 30870487 ; 31170709 ; CRP/CHN09-01
项目资助者: National Basic Research Program of China ; National Science Foundation of China ; International Center for Genetic Engineering and Biotechnology (ICGEB)
WOS记录号: WOS:000337363400011
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67317
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: 1.Peking Univ, Peoples Hosp, Beijing 100871, Peoples R China
2.Capital Med Univ, Beijing, Peoples R China
3.Peking Univ, Sch Life Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China
4.Univ Alabama Birmingham, Birmingham, AL USA
5.Chinese Acad Sci, Beijing, Peoples R China

Recommended Citation:
Xiao, Weichun,Meng, Geng,Zhao, Yanmei,et al. Human Secreted Stabilin-1-Interacting Chitinase-like Protein Aggravates the Inflammation Associated With Rheumatoid Arthritis and Is a Potential Macrophage Inflammatory Regulator in Rodents[J]. ARTHRITIS & RHEUMATOLOGY,2014,66(5):1141-1152.
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