PMID- 15895897 OWN - NLM STAT- MEDLINE DCOM- 20050726 LR - 20170112 IS - 0392-856X (Print) IS - 0392-856X (Linking) VI - 23 IP - 2 DP - 2005 Mar-Apr TI - Monocyte chemoattractant protein-1 activates a regional Th1 immunoresponse in nephritis of MRL/lpr mice. PG - 239-42 AB - 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. FAU - Shimizu, S AU - Shimizu S AD - Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Nakashima, H AU - Nakashima H FAU - Karube, K AU - Karube K FAU - Ohshima, K AU - Ohshima K FAU - Egashira, K AU - Egashira K LA - eng PT - Journal Article PL - Italy TA - Clin Exp Rheumatol JT - Clinical and experimental rheumatology JID - 8308521 RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (RNA, Messenger) RN - 187348-17-0 (Interleukin-12) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - Chemokine CCL2/antagonists & inhibitors/*genetics/metabolism MH - Disease Models, Animal MH - Gene Expression Regulation MH - *Genetic Therapy/methods MH - Humans MH - Interferon-gamma/genetics/metabolism MH - Interleukin-12/genetics/metabolism MH - Kidney Glomerulus/metabolism/pathology MH - Lupus Nephritis/genetics/metabolism/pathology/*therapy MH - Mice MH - Mice, Inbred MRL lpr MH - RNA, Messenger/biosynthesis MH - Th1 Cells/immunology/*metabolism MH - Th2 Cells/immunology/metabolism EDAT- 2005/05/18 09:00 MHDA- 2005/07/27 09:00 CRDT- 2005/05/18 09:00 PHST- 2005/05/18 09:00 [pubmed] PHST- 2005/07/27 09:00 [medline] PHST- 2005/05/18 09:00 [entrez] PST - ppublish SO - Clin Exp Rheumatol. 2005 Mar-Apr;23(2):239-42.