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

S. Shimizu, H. Nakashima, K. Masutani, Y. Inoue, K. Miyake, M. Akahoshi, Y. Tanaka, K. Egashira, H. Hirakata, T. Otsuka, M. Harada

Research output: Contribution to journalArticle

76 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1121-1128
Number of pages8
JournalRheumatology
Volume43
Issue number9
DOIs
Publication statusPublished - Sep 1 2004

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Pharmacology (medical)

Cite this

Shimizu, S., Nakashima, H., Masutani, K., Inoue, Y., Miyake, K., Akahoshi, M., ... Harada, M. (2004). Anti-monocyte chemoattractant protein-1 gene therapy attenuates nephritis in MRL/lpr mice. Rheumatology, 43(9), 1121-1128. https://doi.org/10.1093/rheumatology/keh277