@article {1354346,
	title = {The inhibitory effect of IFN-γ on protease HTRA1 expression in rheumatoid arthritis},
	journal = {J Immunol},
	volume = {193},
	number = {1},
	year = {2014},
	month = {2014 Jul 01},
	pages = {130-8},
	abstract = {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-γ 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-γ 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-γ-deficient mice, HTRA1 expression in the joint tissues was also increased as determined by real-time PCR and Western blots. IFN-γ 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-γ-deficient mice. Mechanistically, IFN-γ 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-γ 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.},
	keywords = {Animals, Arthritis, Rheumatoid, Cell Line, Collagen, Disease Models, Animal, Gene Expression Regulation, Enzymologic, High-Temperature Requirement A Serine Peptidase 1, Humans, Interferon-gamma, Joints, Lipopolysaccharides, Mice, Mice, Knockout, p38 Mitogen-Activated Protein Kinases, Promoter Regions, Genetic, Serine Endopeptidases, STAT1 Transcription Factor},
	issn = {1550-6606},
	doi = {10.4049/jimmunol.1302700},
	author = {Hou, Yuzhu and Lin, Haijiang and Zhu, Linnan and Liu, Zhaoting and Hu, Fanlei and Shi, Jianfeng and Yang, Tao and Shi, Xiaoyun and Guo, Huifang and Tan, Xiaotian and Zhang, Lianfeng and Wang, Qiang and Li, Zhanguo and Zhao, Yong}
}
