@article{APS9708,
author = {Qing QI and Heng LI and Ze-min LIN and Xiao-qian YANG and Feng-hua ZHU and Yu-ting LIU and Mei-juan SHAO and Lu-yao ZHANG and Yan-sheng XU and Yu-xi YAN and Lan-lan SUN and Shi-jun HE and Wei TANG and Jian-ping ZUO},
title = {(5R)-5-hydroxytriptolide ameliorates anti-glomerular basement membrane glomerulonephritis in NZW mice by regulating Fcγ receptor signaling},
journal = {Acta Pharmacologica Sinica},
volume = {39},
number = {1},
year = {2017},
keywords = {},
abstract = {Abstract
(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-α, 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 FcγR-dependent signaling, especially FcγRIIB-mediated downstream kinases, such as BTK. These results demonstrate that LLDT-8 ameliorates anti-GBM glomerulonephritis by regulating the Fcγ receptor signaling.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/9708}
}