Topical administration of reversible SAHH inhibitor ameliorates imiquimod-induced psoriasis-like skin lesions in mice via suppression of TNF-alpha/IFN-gamma-induced inflammatory response in keratinocytes and T cell-derived IL-17

doi:10.1016/j.phrs.2017.11.012

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	Topical administration of reversible SAHH inhibitor ameliorates imiquimod-induced psoriasis-like skin lesions in mice via suppression of TNF-alpha/IFN-gamma-induced inflammatory response in keratinocytes and T cell-derived IL-17
	Lin, Ze-Min 1; Ma, Meng 1; Li, Heng 2,3; Qi, Qing 1; Liu, Yu-Ting 2,3; Yan, Yu-Xi 2,3; Shen, Yun-Fu 1; Yang, Xiao-Qian 2; Zhu, Feng-Hua 2; He, Shi-Jun2,3
刊名	PHARMACOLOGICAL RESEARCH
	2018-03
卷号	129 页码:443-452
关键词	Reversible S-adenosyl-L-homocysteine hydrolase inhibitor Keratinocyte Inflammation Interleukin-17 Imiquimod Psoriasis
ISSN号	1043-6618
DOI	10.1016/j.phrs.2017.11.012
文献子类	Article
英文摘要	DZ2002, a reversible S-adenosyl-L-homocysteine hydrolase (SAHH) inhibitor with immunosuppressive properties and potent therapeutic activity against various autoimmune diseases in mice. The present study was designed to characterize the potential therapeutic effects of DZ2002 on murine model of psoriasis and reveal the correlated mechanisms. In this report, we demonstrated that in vitro, DZ2002 significantly decreased the expression of pro-inflammatory cytokines and adhesion molecule including IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF-alpha and ICAM-1 by inhibiting the phosphorylation of p38 MAPK, ERK and JNK in TNF-alpha/IFN-gamma-stimulated HaCaT human keratinocytes. Topical administration of DZ2002 alleviated the imiquimod (IMQ)-induced psoriasis-like skin lesions and inflammation in mice, the therapeutic effect was comparable with the Calcipotriol. Moreover, the inflammatory skin disorder was restored by DZ2002 treatment characterized by reducing both of the CD3(+) T cell accumulation and the psoriasis specific cytokines expression. Further, we found that DZ2002 improved IMQ-induced splenomegaly and decreased the frequency of splenic IL-17-producing T cells. Our finding offered the convincing evidence that SAHH inhibitor DZ2002 might attenuate psoriasis by simultaneously interfering the abnormal activation and differentiation of keratinocytes and accumulation of IL-17-producing T cells in skin lesions. (C) 2017 Elsevier Ltd. All rights reserved.
资助项目	National Nature Science foundation of China[81402939] ; "Personalized Medicines-Molecular Signature-based Drug Discovery and Development", Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020215] ; "Personalized Medicines-Molecular Signature-based Drug Discovery and Development", Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020107] ; National Basic Research Program of China (973 Program)[2014CB541906]
WOS关键词	L-HOMOCYSTEINE HYDROLASE ; S-ADENOSYLMETHIONINE ; INDUCED ARTHRITIS ; RECENT INSIGHTS ; IN-VIVO ; PATHOGENESIS ; CHEMOKINES ; EXPRESSION ; DERMATITIS ; CYTOKINES
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
WOS记录号	WOS:000428102600041
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279870]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	He, Shi-Jun; Tang, Wei; Zuo, Jian-Ping
作者单位	1.Shanghai Univ Tradit Chinese Med, Lab Immunol & Virol, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Lab Immunopharmacol, Shanghai 201203, Peoples R China; 3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Lin, Ze-Min,Ma, Meng,Li, Heng,et al. Topical administration of reversible SAHH inhibitor ameliorates imiquimod-induced psoriasis-like skin lesions in mice via suppression of TNF-alpha/IFN-gamma-induced inflammatory response in keratinocytes and T cell-derived IL-17[J]. PHARMACOLOGICAL RESEARCH,2018,129:443-452.
APA	Lin, Ze-Min.,Ma, Meng.,Li, Heng.,Qi, Qing.,Liu, Yu-Ting.,...&Zuo, Jian-Ping.(2018).Topical administration of reversible SAHH inhibitor ameliorates imiquimod-induced psoriasis-like skin lesions in mice via suppression of TNF-alpha/IFN-gamma-induced inflammatory response in keratinocytes and T cell-derived IL-17.PHARMACOLOGICAL RESEARCH,129,443-452.
MLA	Lin, Ze-Min,et al."Topical administration of reversible SAHH inhibitor ameliorates imiquimod-induced psoriasis-like skin lesions in mice via suppression of TNF-alpha/IFN-gamma-induced inflammatory response in keratinocytes and T cell-derived IL-17".PHARMACOLOGICAL RESEARCH 129(2018):443-452.