机构：[1]Hongqiao International Institute of Medicine, Shanghai Tongren Hospital, Faculty of Basic Medicine, Shanghai Institute of Immunology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China,[2]Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan, China[3]Present address:Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Persistent activation of mitogen-activated protein kinase (MAPK) is believed to be involved in psoriasis pathogenesis. MAPK phosphatase-1 (MKP-1) is an important negative regulator of MAPK activity, but the cellular and molecular mechanisms of MKP-1 in psoriasis development are largely unknown. In this study, we found that the expression of MKP-1 was decreased in the imiquimod (IMQ)-induced psoriasiform mouse skin. MKP-1-deficient (MKP-1(-/-)) mice were highly susceptible to IMQ-induced skin inflammation, which was associated with increased production of inflammatory cytokines and chemokines. MKP-1 acted on both hematopoietic and non-hematopoietic cells to regulate psoriasis pathogenesis. MKP-1 deficiency in macrophages led to enhanced p38 activation and higher expression of interleukin (IL)-1 beta, CXCL2, and S100a8 upon R848 stimulation. Moreover, MKP-1 deficiency in the non-hematopoietic compartments led to an enhanced IL-22 receptor signaling and higher expression of CXCL1 and CXCL2 upon IMQ treatment. Collectively, our data suggest a critical role for MKP-1 in the regulation of skin inflammation.
基金：
National Natural Science Foundation of China (NSFC) [31670897, 81471528, 91642104, 81671399]; National Key Basic Research Program of ChinaNational Basic Research Program of China [2014CB541803]; Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning; Shanghai Sailing Program [17YF1416600]
第一作者机构：[1]Hongqiao International Institute of Medicine, Shanghai Tongren Hospital, Faculty of Basic Medicine, Shanghai Institute of Immunology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China,
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推荐引用方式(GB/T 7714)：
Zhao Weiheng,Xiao Shuxiu,Li Hongjin,et al.MaPK Phosphatase-1 Deficiency exacerbates the severity of imiquimod-induced Psoriasiform skin Disease[J].FRONTIERS IN IMMUNOLOGY.2018,9:doi:10.3389/fimmu.2018.00569.
APA：
Zhao, Weiheng,Xiao, Shuxiu,Li, Hongjin,Zheng, Tingting,Huang, Jian...&Huang, Gonghua.(2018).MaPK Phosphatase-1 Deficiency exacerbates the severity of imiquimod-induced Psoriasiform skin Disease.FRONTIERS IN IMMUNOLOGY,9,
MLA：
Zhao, Weiheng,et al."MaPK Phosphatase-1 Deficiency exacerbates the severity of imiquimod-induced Psoriasiform skin Disease".FRONTIERS IN IMMUNOLOGY 9.(2018)
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