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学科主题: 药学
题名:
Iminosugar derivative WGN-26 suppresses acute allograft rejection via inhibiting the IFN-gamma/p-STAT1/T-bet signaling pathway
作者: Gao, Xiaoli1,4; Yang, Hua1; Xu, Yangguang1; Xiong, Yulan1,5; Wang, Guannan2,3; Ye, Xinshan2,3; Ye, Jia1
关键词: Iminosugar derivative WGN-26 ; Skin allograft ; IFN-gamma ; p-STAT1/T-bet signaling pathway
刊名: INTERNATIONAL IMMUNOPHARMACOLOGY
发表日期: 2014-12-01
DOI: 10.1016/j.intimp.2014.10.023
卷: 23, 期:2, 页:688-695
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Immunology ; Pharmacology & Pharmacy
研究领域[WOS]: Immunology ; Pharmacology & Pharmacy
关键词[WOS]: IMMUNOSUPPRESSANT DRUGS ; GRAFT-REJECTION ; T-CELLS ; TRANSCRIPTION ; GLUCOSIDASE ; MIGLITOL ; KINASES ; ANALOGS ; STATS ; MICE
英文摘要:

This study aimed to investigate the effect of the iminosugar derivative WGN-26 on suppressing acute allograft rejection and to explore the underlying mechanisms. The results demonstrated that WGN-26 (12, 6 and 3 mg/kg) significantly prolonged the skin allograft survival time in a dose-dependent manner and minimized the pathological changes. The minimum lethal dose was 320 mg/kg. By exploring the potential cellular and molecular mechanisms, we found that WGN-26 dose-dependently inhibited T lymphocyte proliferation, as determined through the single mixed lymphocyte reaction (sMLR) or the ConA-induced T cell proliferation assay in allograft recipients. The FCM results indicated that WGN-26 particularly reduced the percentage of CD3(+)CD4(+) T cells in allograft recipients. After treatment with WGN-26, the secretion of IFN-gamma in allograft recipients was lowered, whereas the IL-4 and IL-17 levels remained stable. Furthermore, we found that WGN-26 inhibited the phosphorylation of STAT1 and accelerated the degradation of T-bet protein in allograft recipients. This study provides the first report that the iminosugar derivative WGN-26 dose-dependently prolongs skin allograft survival and that the possible mechanism is mediated by inhibiting CD4(+) T cell proliferation and suppressing the IFN-gamma/p-STAT1/T-bet signaling pathway. (C) 2014 Elsevier B.V. All rights reserved.

语种: 英语
所属项目编号: NSFC 81470050 ; 91213301 ; 7122097
项目资助者: National Natural Science Foundation of China ; Beijing Natural Science Foundation
WOS记录号: WOS:000346954000043
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/60557
Appears in Collections:北京大学药学院_期刊论文

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作者单位: 1.Peking Univ, Sch Pharmaceut Sci, Dept Mol & Cellular Pharmacol, Beijing 100191, Peoples R China
2.Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
3.Peking Univ, Sch Pharmaceut Sci, Beijing 100191, Peoples R China
4.Beijing Univ Chinese Med, Modem Res Ctr Tradit Chinese Med, Beijing 100029, Peoples R China
5.Peking Univ, Inst Mental Hlth, Beijing 100191, Peoples R China

Recommended Citation:
Gao, Xiaoli,Yang, Hua,Xu, Yangguang,et al. Iminosugar derivative WGN-26 suppresses acute allograft rejection via inhibiting the IFN-gamma/p-STAT1/T-bet signaling pathway[J]. INTERNATIONAL IMMUNOPHARMACOLOGY,2014,23(2):688-695.
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