Abstract
BackgroundFractalkine (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.MethodsForty-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.ResultsThe 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.ConclusionsThe results indicate that MP attenuates LPS-induced FKN expression in kidney of MRL/lpr mice through the NF-kappaB pathway.
Highlights
Fractalkine (FKN) is involved in the occurrence and development of human lupus nephritis
The LPS-induced MRL/lpr mice showed significantly increased serum levels of Blood serum levels of urea nitrogen (BUN) and Cr, and there was a dramatic improvement in renal function in the MP-treated MRL/lpr mice
There was no significant difference of serum BUN and Cr between SC-514-treated MRL/lpr mice and control mice, and between LPS + SC-treated MRL/lpr mice and LPSinduced mice (Fig. 1b and c)
Summary
Fractalkine (FKN) is involved in the occurrence and development of human lupus nephritis. 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. Namely lupus nephritis, is a common and potentially lethal complication of SLE. It involves the production of pathogenic autoantibodies, hypocomplementemia, deposition of immune complexes, inflammation and renal damage [1]. The pathogenesis of lupus nephritis has yet to be determined, increasing lines of evidence have indicated a potential role of cytokines in the development and progression of lupus nephritis [3]
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