TY - JOUR
T1 - Antagonist of monocyte chemoattractant protein 1 ameliorates the initiation and progression of lupus nephritis and renal vasculitis in MRL/lpr mice
AU - Hasegawa, Hitoshi
AU - Kohno, Masashi
AU - Sasaki, Miho
AU - Inoue, Atsushi
AU - Ito, Mitsuko R.
AU - Terada, Miho
AU - Hieshima, Kunio
AU - Maruyama, Hiroki
AU - Miyazaki, Jun Ichi
AU - Yoshie, Osamu
AU - Nose, Masato
AU - Fujita, Shigeru
PY - 2003/9/1
Y1 - 2003/9/1
N2 - Objective. To examine whether chemokine antagonists inhibit the initiation and progression of lupus nephritis in MRL/lpr mice. Methods. NH 2-terminal-truncated monocyte chemoattractant protein 1 (MCP-1)/CCL2 or thymus and activation-regulated chemokine (TARC)/CCL17 analogs were inserted into the pCXN2 expression vector and transfected into a nonmetastatic fibroblastoid cell line, MRL/N-1, established from an MRL/gld mouse. Results. MCP-1 antagonist- or TARC antagonist-transfected MRL/N-1 cells were injected subcutaneously into MRL/lpr mice ages 7 weeks (before the onset of lupus nephritis) and 12 weeks (at the early stage of the disease). After 8 weeks, mice bearing the MCP-1 antagonist showed markedly diminished infiltration of macrophages and T cells, glomerular hypercellularity, glomerulosclerosis, crescent formation, and vasculitis compared with control mice. This seemed to be due to decreased production of interferon-γ and interleukin-2 in the kidney. In contrast, there was no significant difference in renal damage between mice bearing TARC antagonist and control mice. Conclusion. We established a new system using MRL/N-1 cells that allows long-term observation of the effects of chemokine antagonists on lupus nephritis in MRL/lpr mice. We also showed that the MCP-1 antagonist ameliorated the initiation and progression of lupus nephritis and of renal vasculitis, which might provide a new approach to the treatment of the disease.
AB - Objective. To examine whether chemokine antagonists inhibit the initiation and progression of lupus nephritis in MRL/lpr mice. Methods. NH 2-terminal-truncated monocyte chemoattractant protein 1 (MCP-1)/CCL2 or thymus and activation-regulated chemokine (TARC)/CCL17 analogs were inserted into the pCXN2 expression vector and transfected into a nonmetastatic fibroblastoid cell line, MRL/N-1, established from an MRL/gld mouse. Results. MCP-1 antagonist- or TARC antagonist-transfected MRL/N-1 cells were injected subcutaneously into MRL/lpr mice ages 7 weeks (before the onset of lupus nephritis) and 12 weeks (at the early stage of the disease). After 8 weeks, mice bearing the MCP-1 antagonist showed markedly diminished infiltration of macrophages and T cells, glomerular hypercellularity, glomerulosclerosis, crescent formation, and vasculitis compared with control mice. This seemed to be due to decreased production of interferon-γ and interleukin-2 in the kidney. In contrast, there was no significant difference in renal damage between mice bearing TARC antagonist and control mice. Conclusion. We established a new system using MRL/N-1 cells that allows long-term observation of the effects of chemokine antagonists on lupus nephritis in MRL/lpr mice. We also showed that the MCP-1 antagonist ameliorated the initiation and progression of lupus nephritis and of renal vasculitis, which might provide a new approach to the treatment of the disease.
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U2 - 10.1002/art.11231
DO - 10.1002/art.11231
M3 - Article
C2 - 13130475
AN - SCOPUS:0141564974
VL - 48
SP - 2555
EP - 2566
JO - Arthritis and Rheumatism
JF - Arthritis and Rheumatism
SN - 0004-3591
IS - 9
ER -