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(5R)-5-hydroxytriptolide ameliorates anti-glomerular basement membrane glomerulonephritis in NZW mice by regulating Fc gamma receptor signaling 期刊论文

编号：

1d1ae549-7c7e-45e1-a4ca-789f2bfb7c02
作者：

Qi, Qing#^[1,2]Li, Heng^[2,3];Lin, Zemin^[2];Yang, Xiaoqian^[2];Zhu, Fenghua^[2];Liu, Yuting^[2,3];Shao, Meijuan^[1,2];Zhang, Luyao^[2,3];Xu, Yansheng^[1,2];Yan, Yuxi^[2,3];Sun, Lanlan^[2,4];He, Shijun*^[2]Tang, Wei*^[2,3]Zuo, Jianping(左建平)*^[1,2,3]
语种：

英文
期刊：

ACTA PHARMACOLOGICA SINICA ISSN：1671-4083 2018 年 39 卷 1 期 (107 - 116) ; JAN
收录：
关键词：

triptolide (5R)-5-hydroxytriptolide (LLDT-8) prednisolone glomerulonephritis immune complexes inflammation Fc gamma receptor signaling
摘要：

(5R)-5-hydroxytriptolide (LLDT-8) is a novel triptolide analog that has been identified as a promising candidate for treating autoimmune diseases and has been shown to be effective in treating murine collagen-induced arthritis and lupus nephritis. In the present study, we investigated the therapeutic effect and possible mechanism of action of LLDT-8 in a murine anti-glomerular basement membrane (GBM) glomerulonephritis model. NZW mice were injected with rabbit anti-GBM serum (500 mu L, ip). The mice were orally treated with LLDT-8 (0.125 mg/kg, every other day) or a positive control prednisolone (2 mg/kg every day) for 14 d. Blood and urine samples as well as spleen and kidney tissues were collected for analyses. LLDT-8 treatment did not affect the generation of mouse anti-rabbit antibodies. LLDT-8 significantly reversed established proteinuria, improved renal histopathology and attenuated renal dysfunction in glomerulonephritis mice. Furthermore, LLDT-8 inhibited inflammation in the kidney evidenced by significantly decreasing C3 and IgG deposition, reducing the levels of the pathogenic cytokines TNF-alpha, IL-6, IL-17, and IFN-gamma, and reducing related chemokine expression and leukocyte infiltration in kidneys. Moreover, LLDT-8 treatment significantly increased the expression of Fc gamma RIIB in the kidney and spleen. In addition, the treatment restored the reduced expression of Fc gamma RIIB on the surface of kidney effector cells, CD11b(+) cells, and interfered with Fc gamma R-dependent signaling, especially Fc gamma RIIB-mediated downstream kinases, such as BTK. These results demonstrate that LLDT-8 ameliorates anti-GBM glomerulonephritis by regulating the Fc gamma receptor signaling.
推荐引用方式
GB/T 7714：

Qi Qing,Li Heng,Lin Ze-min, et al. (5R)-5-hydroxytriptolide ameliorates anti-glomerular basement membrane glomerulonephritis in NZW mice by regulating Fc gamma receptor signaling [J].ACTA PHARMACOLOGICA SINICA,2018,39(1):107-116.
APA：

Qi Qing,Li Heng,Lin Ze-min,Yang Xiao-qian,&Zuo Jian-ping.(2018).(5R)-5-hydroxytriptolide ameliorates anti-glomerular basement membrane glomerulonephritis in NZW mice by regulating Fc gamma receptor signaling .ACTA PHARMACOLOGICA SINICA,39(1):107-116.
MLA：

Qi Qing, et al. "(5R)-5-hydroxytriptolide ameliorates anti-glomerular basement membrane glomerulonephritis in NZW mice by regulating Fc gamma receptor signaling" .ACTA PHARMACOLOGICA SINICA 39,1(2018):107-116.
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