Methylprednisolone attenuates lipopolysaccharide-induced Fractalkine expression in kidney of Lupus-prone MRL/lpr mice through the NF-kappaB pathway.
Methylprednisolone attenuates lipopolysaccharide-induced Fractalkine expression in kidney of Lupus-prone MRL/lpr mice through the NF-kappaB pathway.
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甲基泼尼松龙通过 NF-kappaB 途径减弱狼疮倾向 MRL/lpr 小鼠肾脏中脂多糖诱导的 Fractalkine 表达
DOI：
10.1186/s12882-015-0145-y
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发表时间：
2015-08-27
期刊：
影响因子：
2.3
通讯作者：
Pinhu L
中科院分区：
文献类型：
--
作者：
You Y;Qin Y;Lin X;Yang F;Li J;Sooranna SR;Pinhu L
Fractalkine（FKN）参与了人类狼疮性肾炎的发生和发展。已知其在体内被作为刺激物的脂多糖（LPS）上调。MRL/lpr小鼠已被用作研究狼疮性肾炎的体内模型。甲基强的松龙（MP）广泛用于临床治疗狼疮性肾炎等进行性肾小球疾病。本研究旨在探讨LPS诱导MRL/lpr小鼠FKN表达的机制，并确定是否有其他分子机制参与MP作用的信号通路。将48只12周龄的雌性MRL/lpr小鼠随机分为6组。每组接受不同的治疗，共8周，每周两次腹腔注射（1）MP（MP处理小鼠），（2）SC-514（SC-514诱导的小鼠），（3）生理盐水和单次注射LPS（4）MP和单次注射LPS（LPS + MP小鼠），（5）SC-514和单次注射LPS（LPS + SC小鼠）和（6）生理盐水（对照小鼠）。数据分析采用单因素方差分析，P值<0.05视为具有统计学意义。qPCR检测FKN和NF-κ B p65 mRNA的表达。免疫组化法检测FKN蛋白的表达，Western blot法检测NF-κ B p65的活化。LPS诱导的小鼠肾脏中FKN的表达显著增加，这是由NF-κB p65表达增加和NF-κ B磷酸化p65增加介导的。MP能减少MRL/lpr小鼠的蛋白尿，减轻肾损害。MP和NF-κ B抑制剂SC-514抑制LPS诱导的FKN表达增加和NF-κ B活化。结果表明，MP通过NF-κ B途径减弱LPS诱导的MRL/lpr小鼠肾脏中FKN的表达。
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.