抗单核细胞趋化蛋白-1基因疗法减轻MRL/lpr小鼠的肾炎。
Anti-monocyte chemoattractant protein-1 gene therapy attenuates nephritis in MRL/lpr mice.
作者信息
Shimizu S, Nakashima H, Masutani K, Inoue Y, Miyake K, Akahoshi M, Tanaka Y, Egashira K, Hirakata H, Otsuka T, Harada M
机构信息
Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
出版信息
Rheumatology (Oxford). 2004 Sep;43(9):1121-8. doi: 10.1093/rheumatology/keh277. Epub 2004 Jun 22.
OBJECTIVE
Monocyte chemoattractant protein-1 (MCP-1) is up-regulated and recruits and activates inflammatory cells in human diffuse proliferative lupus nephritis (DPLN) and in nephritis of lupus model MRL/lpr mice. The aim of this study was to examine whether anti-MCP-1 gene therapy inhibits the progression of nephritis in MRL/lpr mice.
METHOD
An NH(2)-terminal deletion mutant of the MCP-1 gene, 7ND, was injected into skeletal muscles of MRL/lpr mice with advanced stage nephritis to blockade MCP-1 and its receptor (CCR2) signalling pathway.
RESULT
Histological findings of kidneys in treated mice, which received more than four injections of 7ND, showed that protection against renal injury resulted from reduced infiltration of leucocytes. Therefore, this therapy has been shown to prolong the life span of MRL/lpr mice.
CONCLUSION
Anti-MCP-1 gene therapy is specifically effective in the localized inflammatory region. The data presented here indicate that this anti-MCP-1 gene therapy may be effective adjunct in the management of DPLN.
目的
单核细胞趋化蛋白-1（MCP-1）在人类弥漫性增殖性狼疮性肾炎（DPLN）及狼疮模型MRL/lpr小鼠的肾炎中表达上调，并募集和激活炎症细胞。本研究旨在探讨抗MCP-1基因治疗是否能抑制MRL/lpr小鼠肾炎的进展。
方法
将MCP-1基因的氨基末端缺失突变体7ND注射到患有晚期肾炎的MRL/lpr小鼠的骨骼肌中，以阻断MCP-1及其受体（CCR2）信号通路。
结果
接受超过四次7ND注射的治疗小鼠的肾脏组织学检查结果显示，对肾损伤的保护作用源于白细胞浸润减少。因此，该治疗已被证明可延长MRL/lpr小鼠的寿命。
结论
抗MCP-1基因治疗在局部炎症区域具有特异性疗效。本文提供的数据表明，这种抗MCP-1基因治疗可能是DPLN治疗中的有效辅助手段。
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