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学科主题: 临床医学
题名:
The Inhibitory Effect of IFN-gamma on Protease HTRA1 Expression in Rheumatoid Arthritis
作者: Hou, Yuzhu1,2; Lin, Haijiang3; Zhu, Linnan1,2; Liu, Zhaoting1; Hu, Fanlei4; Shi, Jianfeng1,2; Yang, Tao1,2; Shi, Xiaoyun1,5; Guo, Huifang6; Tan, Xiaotian1; Zhang, Lianfeng7,8; Wang, Qiang1; Li, Zhanguo4; Zhao, Yong1,2
刊名: JOURNAL OF IMMUNOLOGY
发表日期: 2014-07-01
DOI: 10.4049/jimmunol.1302700
卷: 193, 期:1, 页:130-138
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Immunology
研究领域[WOS]: Immunology
关键词[WOS]: COLLAGEN-INDUCED ARTHRITIS ; SERINE-PROTEASE ; DEFICIENT MICE ; LONG-TERM ; CARTILAGE ; GENE ; MACROPHAGES ; LPS ; SUSCEPTIBILITY ; DEGENERATION
英文摘要:

The high temperature requirement A1 (HTRA1) is a potent protease involved in many diseases, including rheumatoid arthritis (RA). However, the regulatory mechanisms that control HTRA1 expression need to be determined. In this study, we demonstrated that IFN-gamma significantly inhibited the basal and LPS-induced HTRA1 expression in fibroblasts and macrophages, which are two major cells for HTRA1 production in RA. Importantly, the inhibitory effect of IFN-gamma on HTRA1 expression was evidenced in collagen-induced arthritis (CIA) mouse models and in human RA synovial cells. In parallel with the enhanced CIA incidence and pathological changes in IFN-gamma-deficient mice, HTRA1 expression in the joint tissues was also increased as determined by real-time PCR and Western blots. IFN-gamma deficiency increased the incidence of CIA and the pathological severity in mice. Neutralization of HTRA1 by Ab significantly reversed the enhanced CIA frequency and severity in IFN-gamma-deficient mice. Mechanistically, IFN-gamma negatively controls HTRA1 expression through activation of p38 MAPK/STAT1 pathway. Dual luciferase reporter assay and chromatin immunoprecipitation analysis showed that STAT1 could directly bind to HTRA1 promoter after IFN-gamma stimulation. This study offers new insights into the molecular regulation of HTRA1 expression and its role in RA pathogenesis, which may have significant impact on clinical therapy for RA and possibly other HTRA1-related diseases, including osteoarthritis, age-related macular degeneration, and cancer.

语种: 英语
所属项目编号: 2010CB945301 ; 2011CB710900 ; 2010CB529100 ; C81130055 ; U0832003 ; YSCX2-YW-238
项目资助者: National Basic Research Program of China ; National Natural Science Foundation of China ; Knowledge Innovation Program of Chinese Academy of Sciences ; State Administration of Foreign Experts Affairs of Chinese Academy of Sciences International Partnership Program for Creative Research Teams
WOS记录号: WOS:000338438900018
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/61939
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.Chinese Acad Sci, Inst Zool, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100101, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA
4.Peking Univ, Peoples Hosp, Clin Immunol Ctr, Dept Rheumatol & Immunol, Beijing 100044, Peoples R China
5.Chinese Peoples Armed Police Forces, Gen Hosp, Beijing 100039, Peoples R China
6.Hebei Med Univ, Hosp 2, Dept Rheumatol, Shijiazhuang 050000, Peoples R China
7.Chinese Acad Med Sci, Minist Hlth, Key Lab Human Dis Comparat Med, Beijing 100021, Peoples R China
8.Chinese Acad Med Sci, Inst Lab Anim Sci, Beijing 100021, Peoples R China
9.Peking Union Med Coll, Beijing 100021, Peoples R China

Recommended Citation:
Hou, Yuzhu,Lin, Haijiang,Zhu, Linnan,et al. The Inhibitory Effect of IFN-gamma on Protease HTRA1 Expression in Rheumatoid Arthritis[J]. JOURNAL OF IMMUNOLOGY,2014,193(1):130-138.
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