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
文献类型：期刊论文
| 作者 | Lin, Ze-Min1; Ma, Meng1; Li, Heng2,3; Qi, Qing1; Liu, Yu-Ting2,3; Yan, Yu-Xi2,3; Shen, Yun-Fu1; Yang, Xiao-Qian2; Zhu, Feng-Hua2; He, Shi-Jun2,3
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| 刊名 | PHARMACOLOGICAL RESEARCH
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| 出版日期 | 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. |
| WOS关键词 | L-HOMOCYSTEINE HYDROLASE ; S-ADENOSYLMETHIONINE ; INDUCED ARTHRITIS ; RECENT INSIGHTS ; IN-VIVO ; PATHOGENESIS ; CHEMOKINES ; EXPRESSION ; DERMATITIS ; CYTOKINES |
| 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研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000428102600041 |
| 出版者 | ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD |
| 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. |
入库方式： OAI收割
来源：上海药物研究所
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