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学科主题临床医学
The Inhibitory Effect of IFN-gamma on Protease HTRA1 Expression in Rheumatoid Arthritis
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
2014-07-01
DOI10.4049/jimmunol.1302700
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
WOS记录号WOS:000338438900018
项目编号2010CB945301 ; 2011CB710900 ; 2010CB529100 ; C81130055 ; U0832003 ; YSCX2-YW-238
资助机构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
引用统计
被引频次:12[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/61939
专题北京大学第二临床医学院
北京大学第二临床医学院_风湿免疫科
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
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GB/T 7714
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.
APA Hou, Yuzhu.,Lin, Haijiang.,Zhu, Linnan.,Liu, Zhaoting.,Hu, Fanlei.,...&Zhao, Yong.(2014).The Inhibitory Effect of IFN-gamma on Protease HTRA1 Expression in Rheumatoid Arthritis.JOURNAL OF IMMUNOLOGY,193(1),130-138.
MLA Hou, Yuzhu,et al."The Inhibitory Effect of IFN-gamma on Protease HTRA1 Expression in Rheumatoid Arthritis".JOURNAL OF IMMUNOLOGY 193.1(2014):130-138.
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