Monocyte chemoattractant protein-1 activates a regional Th1 immunoresponse in nephritis of MRL/lpr mice.
OBJECTIVE
Monocyte chemoattractant protein-1 (MCP-1) is upregulated and recruits and activates inflammatory cells in nephritis of MRL lpr mice. It has been shown that anti-MCP-1 gene therapy is specifically effective in nephritis, while it was apparent that an imbalance towards Th1 predominance accelerates nephritis in MRL/lpr mice. The aim of this study was to clarify whether blockade of the MCP-1 signal by anti-MCP-1 gene therapy influences the Th1/Th2 balance in MRL/lpr mice.


METHODS
An NH2-terminal deletion mutant of the MCP-1 gene (7ND) was injected into the skeletal muscles of MRL/Ipr mice with advanced stage nephritis to suppress MCP-1 and its receptor (CCR2) signaling pathway. We evaluated the local tissue production of cytokines in splenocytes and microdissected infiltrating cells within the glomeruli or interstitium.


RESULTS
Although the production of cytokines in splenocytes was not influenced by anti-MCP-1 gene therapy, kidney glomeruli IL-12 mRNA production and interstitium-infiltrating cell production of IL-12 and IFN-gamma mRNA were significantly reduced.


CONCLUSIONS
The blockade of MCP-1 gene therapy does not influence helper T cell polarization, but acts directly on the regional Th1 immunoreaction in MRL/lpr mice.
Shimizu
S
S
Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Nakashima
H
H
Karube
K
K
Ohshima
K
K
Egashira
K
K
D000818:Animals; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D008181:Lupus Nephritis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D012333:RNA, Messenger / Q000096:biosynthesis; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D012333:RNA, Messenger; D018664:Interleukin-12; D007371:Interferon-gamma