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Updated: Aug 18, 2026
Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
Published on: June 8, 2022
Monocyte chemoattractant protein-1 activates a regional Th1 immunoresponse in nephritis of MRL/lpr mice
S Shimizu1, H Nakashima, K Karube
1Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
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.
Method:
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.
Result:
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.
Conclusion:
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.
