(5R)-5-hydroxytriptolide ameliorates lupus nephritis in MRL/lpr mice by preventing infiltration of immune cells

doi:10.1152/ajprenal.00649.2016

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	(5R)-5-hydroxytriptolide ameliorates lupus nephritis in MRL/lpr mice by preventing infiltration of immune cells
	Zhang, Lu-yao 1,2; Li, Heng 1,2; Wu, Yan-wei 2; Cheng, Lei 1,2; Yan, Yu-xi 1,2; Yang, Xiao-qian 2; Zhu, Feng-hua 2; He, Shi-jun2 ; Tang, Wei2 ; Zuo, Jian-ping1,2
刊名	AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
	2017-04
卷号	312 期号:4 页码:F769-F777
关键词	systemic lupus erythematosus inflammation chemokines
ISSN号	1931-857X
DOI	10.1152/ajprenal.00649.2016
文献子类	Article
英文摘要	(5R)-5-hydroxytriptolide (LLDT-8), a triptolide derivative with low toxicity, was previously reported to have strong immunosuppressive effects both in vitro and in vivo, but it remains unknown whether LLDT-8 has a therapy effect on systemic lupus erythematosus. In this study, we aimed to investigate the therapeutic effects of LLDT-8 on lupus nephritis in MRL/lpr mice, a model of systemic lupus erythematosus. Compared with the vehicle group, different clinical parameters were improved upon LLDT-8 treatment as follows: prolonged life span of mice, decreased proteinuria, downregulated blood urea nitrogen and serum creatinine, reduced glomerular IgG deposits, and ameliorated histopathology. A decreased expression of the inflammatory cytokines IFN-gamma, IL-17, IL-6, and TNF-alpha was also observed in the kidney of LLDT-8 treated MRL/lpr mice. Moreover, infiltration of T cells in the kidney was mitigated after LLDT-8 treatment, corresponding with decreased expression of related chemokines IP-10, Mig, and RANTES in the kidney. The proportion of macrophage and neutrophil cells and related chemokines expression was also reduced in kidneys of LLDT-8-treated mice. In the human proximal tubule epithelial cell line and mouse mesangial cell line, consistent with our in vivo experimental results, LLDT-8 suppressed the expression of related chemokines and IL-6. In summary, LLDT-8 has a therapeutic benefit for lupus nephritis via suppressing chemokine expression and inhibiting immune cell infiltration in kidneys of MRL/lpr mice.
资助项目	National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program," China[2014ZX09101002-001]
WOS关键词	WILFORDII HOOK-F ; EXPERIMENTAL MEMBRANOUS NEPHROPATHY ; IN-VITRO ; T-CELLS ; CYTOKINE EXPRESSION ; INTERFERON-GAMMA ; KIDNEY-DISEASE ; TRIPTOLIDE ; ERYTHEMATOSUS ; GLOMERULONEPHRITIS
WOS研究方向	Physiology ; Urology & Nephrology
语种	英语
出版者	AMER PHYSIOLOGICAL SOC
WOS记录号	WOS:000404360100006
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272711]
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	Zuo, Jian-ping
作者单位	1.Univ Chinese Acad Sci, Beijing, Peoples R China 2.Chinese Acad Sci, Lab Immunopharmacol, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai, Peoples R China;
推荐引用方式 GB/T 7714	Zhang, Lu-yao,Li, Heng,Wu, Yan-wei,et al. (5R)-5-hydroxytriptolide ameliorates lupus nephritis in MRL/lpr mice by preventing infiltration of immune cells[J]. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY,2017,312(4):F769-F777.
APA	Zhang, Lu-yao.,Li, Heng.,Wu, Yan-wei.,Cheng, Lei.,Yan, Yu-xi.,...&Zuo, Jian-ping.(2017).(5R)-5-hydroxytriptolide ameliorates lupus nephritis in MRL/lpr mice by preventing infiltration of immune cells.AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY,312(4),F769-F777.
MLA	Zhang, Lu-yao,et al."(5R)-5-hydroxytriptolide ameliorates lupus nephritis in MRL/lpr mice by preventing infiltration of immune cells".AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY 312.4(2017):F769-F777.