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Rheumatology Advance Access published online on June 22, 2004
Rheumatology, doi:10.1093/rheumatology/keh277
Rheumatology © British Society for Rheumatology 2004; all rights reserved
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Received March 19, 2004
Accepted May 17, 2004

Original Papers

Anti-monocyte chemoattractant protein-1 gene therapy attenuates nephritis in MRL/lpr mice

S. Shimizu 1, H. Nakashima 1*, K. Masutani 2, Y. Inoue 1, K. Miyake 1, M. Akahoshi 3, Y. Tanaka 1, K. Egashira 4, H. Hirakata 2, T. Otsuka 1, M. Harada 1

1 Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
2 Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
3 Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Laboratory for Genetics of Allergic Diseases, SNP Research Center, RIKEN Yokohama Institute, The Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan
4 Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

* To whom correspondence should be addressed. E-mail: hnakashi{at}intmed1.med.kyushu-u.ac.jp.


  Abstract

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 NH2-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.

Keywords: Monocyte chemoattractant protein-1 (MCP-1); Systemic lupus erythematosus (SLE); MRL/lpr mice; Diffuse proliferative lupus nephritis (DPLN); Gene therapy
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