TY - JOUR
T1 - Anti-monocyte chemoattractant protein-1 gene therapy attenuates nephritis in MRL/lpr mice
AU - Shimizu, S.
AU - Nakashima, H.
AU - Masutani, K.
AU - Inoue, Y.
AU - Miyake, K.
AU - Akahoshi, M.
AU - Tanaka, Y.
AU - Egashira, K.
AU - Hirakata, H.
AU - Otsuka, T.
AU - Harada, M.
PY - 2004/9
Y1 - 2004/9
N2 - 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.
AB - 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.
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U2 - 10.1093/rheumatology/keh277
DO - 10.1093/rheumatology/keh277
M3 - Article
C2 - 15213333
AN - SCOPUS:4544266604
SN - 1462-0324
VL - 43
SP - 1121
EP - 1128
JO - Rheumatology and Rehabilitation
JF - Rheumatology and Rehabilitation
IS - 9
ER -