PMID- 15213333 OWN - NLM STAT- MEDLINE DCOM- 20041101 LR - 20121115 IS - 1462-0324 (Print) IS - 1462-0324 (Linking) VI - 43 IP - 9 DP - 2004 Sep TI - Anti-monocyte chemoattractant protein-1 gene therapy attenuates nephritis in MRL/lpr mice. PG - 1121-8 AB - 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. METHOD: 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. RESULT: 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. CONCLUSION: 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. FAU - Shimizu, S AU - Shimizu S AD - Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan. FAU - Nakashima, H AU - Nakashima H FAU - Masutani, K AU - Masutani K FAU - Inoue, Y AU - Inoue Y FAU - Miyake, K AU - Miyake K FAU - Akahoshi, M AU - Akahoshi M FAU - Tanaka, Y AU - Tanaka Y FAU - Egashira, K AU - Egashira K FAU - Hirakata, H AU - Hirakata H FAU - Otsuka, T AU - Otsuka T FAU - Harada, M AU - Harada M LA - eng PT - Journal Article DEP - 20040622 PL - England TA - Rheumatology (Oxford) JT - Rheumatology (Oxford, England) JID - 100883501 RN - 0 (Antibodies, Antinuclear) RN - 0 (CCR2 protein, human) RN - 0 (Ccr2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Immunoglobulin G) RN - 0 (Receptors, CCR2) RN - 0 (Receptors, Chemokine) RN - 9007-49-2 (DNA) SB - IM MH - Animals MH - Antibodies, Antinuclear/blood MH - Chemokine CCL2/biosynthesis/blood/*genetics MH - DNA/immunology MH - Genetic Therapy/*methods MH - Immunoglobulin G/analysis MH - Kidney/immunology/pathology MH - Leukocytes/immunology MH - Lung/immunology/pathology MH - Lupus Nephritis/genetics/pathology/*therapy MH - Lymphatic Diseases/genetics/pathology/therapy MH - Mice MH - Mice, Inbred MRL lpr MH - Muscle, Skeletal MH - Mutation MH - Proteinuria/immunology MH - Receptors, CCR2 MH - Receptors, Chemokine/genetics MH - Signal Transduction/genetics MH - Splenomegaly/genetics/pathology/therapy MH - Transgenes/genetics EDAT- 2004/06/24 05:00 MHDA- 2004/11/02 09:00 CRDT- 2004/06/24 05:00 PHST- 2004/06/24 05:00 [pubmed] PHST- 2004/11/02 09:00 [medline] PHST- 2004/06/24 05:00 [entrez] AID - keh277 [pii] AID - 10.1093/rheumatology/keh277 [doi] PST - ppublish SO - Rheumatology (Oxford). 2004 Sep;43(9):1121-8. doi: 10.1093/rheumatology/keh277. Epub 2004 Jun 22.