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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Shimizu
S
S
Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
Nakashima
H
H
Masutani
K
K
Inoue
Y
Y
Miyake
K
K
Akahoshi
M
M
Tanaka
Y
Y
Egashira
K
K
Hirakata
H
H
Otsuka
T
T
Harada
M
M
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D004247:DNA / Q000276:immunology; D015316:Genetic Therapy / Q000379:methods*; D007074:Immunoglobulin G / Q000032:analysis; D007668:Kidney / Q000276:immunology / Q000473:pathology; D007962:Leukocytes / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008181:Lupus Nephritis / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008206:Lymphatic Diseases / Q000235:genetics / Q000473:pathology / Q000628:therapy; D051379:Mice; D019463:Mice, Inbred MRL lpr; D018482:Muscle, Skeletal; D009154:Mutation; D011507:Proteinuria / Q000276:immunology; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013163:Splenomegaly / Q000235:genetics / Q000473:pathology / Q000628:therapy; D019076:Transgenes / Q000235:genetics
D000974:Antibodies, Antinuclear; C515334:CCR2 protein, human; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D007074:Immunoglobulin G; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D004247:DNA