(5R)-5-hydroxytriptolide ameliorates anti-glomerular basement membrane glomerulonephritis in NZW mice by regulating Fcy receptor signaling

	(5R)-5-hydroxytriptolide ameliorates anti-glomerular basement membrane glomerulonephritis in NZW mice by regulating Fcy receptor signaling
	Qi Qing 1; Li Heng 2; Lin Zemin 1; Yang Xiaoqian 2; Zhu Fenghua 2; Liu Yuting 2; Shao Meijuan 1; Zhang Luyao 2; Yanshengxu 1; Yan Yuxi 2
刊名	Acta Pharmacologica Sinica
	2018
卷号	39 期号:1 页码:107
关键词	triptolide (5R)-5-hydroxytriptolide (LLDT-8) prednisolone glomerulonephritis immune complexes inflammation Fcy receptor signaling
ISSN号	1671-4083
英文摘要	(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 μL,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-a, IL-6,IL-17, and IFN-γ,and reducing related chemokine expression and leukocyte infiltration in kidneys. Moreover, LLDT-8 treatment significantly increased the expression of FcγRIIB in the kidney and spleen. In addition, the treatment restored the reduced expression of FcγRIIB on the surface of kidney effector cells,CD11b~+ cells, and interfered with FcyR-dependent signaling, especially FcyRIIB-mediated downstream kinases, such as BTK. These results demonstrate that LLDT-8 ameliorates anti-GBM glomerulonephritis by regulating the Fcy receptor signaling.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/293363]
专题	中国科学院上海药物研究所
作者单位	1.上海中医药大学 2.中国科学院上海药物研究所
推荐引用方式 GB/T 7714	Qi Qing,Li Heng,Lin Zemin,et al. (5R)-5-hydroxytriptolide ameliorates anti-glomerular basement membrane glomerulonephritis in NZW mice by regulating Fcy receptor signaling[J]. Acta Pharmacologica Sinica,2018,39(1):107.
APA	Qi Qing.,Li Heng.,Lin Zemin.,Yang Xiaoqian.,Zhu Fenghua.,...&Jianpingzuo.(2018).(5R)-5-hydroxytriptolide ameliorates anti-glomerular basement membrane glomerulonephritis in NZW mice by regulating Fcy receptor signaling.Acta Pharmacologica Sinica,39(1),107.
MLA	Qi Qing,et al."(5R)-5-hydroxytriptolide ameliorates anti-glomerular basement membrane glomerulonephritis in NZW mice by regulating Fcy receptor signaling".Acta Pharmacologica Sinica 39.1(2018):107.