Details

Autor(en) / Beteiligte

• Qing QI
• Heng LI
• Ze-min LIN
• Xiao-qian YANG
• Feng-hua ZHU
• Yu-ting LIU
• Mei-juan SHAO
• Lu-yao ZHANG
• Yan-sheng XU
• Yu-xi YAN
• Lan-lan SUN
• Shi-jun HE
• Wei TANG
• Jian-ping ZUO

Titel

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

Ist Teil von

• 中国药理学报：英文版, 2018, Vol.39 (1), p.107-116

Erscheinungsjahr

2018

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• （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 FcγR11B in the kidney and spleen. In addition, the treatment restored the reduced expression of FcyRIIB 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 Fcγ receptor signaling.