Antagonist of Monocyte Chemoattractant Protein 1 Ameliorates the Initiation and Progression of Lupus Nephritis and Renal Vasculitis in MRL/lpr Mice.
Hasegawa, Hitoshi 1; Kohno, Masashi 1; Sasaki, Miho 1; Inoue, Atsushi 1; Ito, Mitsuko R. 1; Terada, Miho 1; Hieshima, Kunio 2; Maruyama, Hiroki 3; Miyazaki, Jun-ichi 4; Yoshie, Osamu 2; Nose, Masato 1; Fujita, Shigeru 1
[Article] Arthritis & Rheumatism. 48(9):2555-2566, September 2003.

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Objective: To examine whether chemokine antagonists inhibit the initiation and progression of lupus nephritis in MRL/lpr mice.

Methods: NH2-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-[gamma] 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.

(C) 2003, American College of Rheumatology