Benvenuti ad Adobe GoLive 6

Monocyte chemoattractant protein-1 activates a regional Th1 immuno-response in nephritis of MRL/lpr mice

S. Shimizu¹, H. Nakashima¹, K. Karube^1,2, K. Ohshima², K. Egashira³

¹Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka; ²Department of Pathology, Faculty of Medicine, Fukuoka University, Fukuoka; ³Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

ABSTRACT
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/lpr 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-g 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.

Key words
Monocyte chemoattractant protein-1(MCP-1), MRL/lpr mice, Th1/Th2 balance, SLE.

Please address correspondence and reprint requests to: Hitoshi Nakashima, MD, PhD, Dept. of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
E-mail: hnakashi@intmed1.med.kyushu-u.ac.jp