Methylprednisolone attenuates lipopolysaccharide-induced Fractalkine expression in kidney of Lupus-prone MRL/lpr mice through the NF-kappaB pathway.

Yanwu You, Yueqiu Qin, Xu Lin, Fafen Yang, Jun Li, Suren R Sooranna, Liao Pinhu

文献索引：BMC Nephrol. 16 , 148, (2015)

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摘要

Fractalkine (FKN) is involved in the occurrence and development of human lupus nephritis. It is known to be upregulated by lipopolysaccharide (LPS) as a stimulus in vivo. MRL/lpr mice have been used as an in vivo model to study lupus nephritis. Methylprednisolone (MP) is used widely in the clinical treatment of progressive glomerular diseases such as lupus nephritis. The aim of this study is to explore the mechanism of LPS induced FKN expression and to determine whether other molecular mechanisms contribute to the signaling pathway of MP action in MRL/lpr mice.Forty-eight female MRL/lpr mice at 12 weeks of age were randomly distributed into six groups. Each group received various treatments for 8 weeks by receiving twice weekly intraperitoneal injections of (1) MP (MP-treated mice), of (2) SC-514 (SC-514-induced mice), of (3) normal saline and a single injection of LPS (LPS-induced mice), of (4) MP and a single injection of LPS (LPS + MP mice), of (5) SC-514 and a single injection of LPS (LPS + SC mice) and of (6) normal saline (control mice). One-way ANOVA was used for data analysis and P value <0.05 was considered statistically significantly.The expression of FKN and NF-kappaB p65 mRNA was detected by qPCR. The expression of FKN protein and the activation of NF-kappaB p65 were detected by immunohistochemistry and western blots respectively. The expression of FKN in the kidney of LPS induced mice was significantly increased and this was mediated by increased expression of NF-κB p65 and an increase in NF-kappaB phospho-p65. MP reduced proteinuria and ameliorated the renal damage in MRL/lpr mice. MP as well as the NF-kappaB inhibitor, SC-514, inhibited the LPS-induced increase of expression of FKN and the activation of NF-kappaB.The results indicate that MP attenuates LPS-induced FKN expression in kidney of MRL/lpr mice through the NF-kappaB pathway.