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Iminosugar derivative WGN-26 suppresses acute allograft rejection via inhibiting the IFN-gamma/p-STAT1/T-bet signaling pathway
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
2014-12-01
DOI10.1016/j.intimp.2014.10.023
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
WOS记录号WOS:000346954000043
项目编号NSFC 81470050 ; 91213301 ; 7122097
资助机构National Natural Science Foundation of China ; Beijing Natural Science Foundation
引用统计
被引频次:5[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/60557
专题北京大学药学院
北京大学药学院_药物化学系
北京大学药学院_分子与细胞药理学系
北京大学精神卫生研究所_药房
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
推荐引用方式
GB/T 7714
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.
APA Gao, Xiaoli.,Yang, Hua.,Xu, Yangguang.,Xiong, Yulan.,Wang, Guannan.,...&Ye, Jia.(2014).Iminosugar derivative WGN-26 suppresses acute allograft rejection via inhibiting the IFN-gamma/p-STAT1/T-bet signaling pathway.INTERNATIONAL IMMUNOPHARMACOLOGY,23(2),688-695.
MLA Gao, Xiaoli,et al."Iminosugar derivative WGN-26 suppresses acute allograft rejection via inhibiting the IFN-gamma/p-STAT1/T-bet signaling pathway".INTERNATIONAL IMMUNOPHARMACOLOGY 23.2(2014):688-695.
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