Open AccessAntagonist of monocyte chemoattractant protein 1 ameliorates the initiation and progression of lupus nephritis and renal vasculitis in MRL/lpr mice
Author(s) -
Hasegawa Hitoshi,
Kohno Masashi,
Sasaki Miho,
Inoue Atsushi,
Ito Mitsuko R.,
Terada Miho,
Hieshima Kunio,
Maruyama Hiroki,
Miyazaki Junichi,
Yoshie Osamu,
Nose Masato,
Fujita Shigeru
Publication year - 2003
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.11231
Subject(s) - lupus nephritis , chemokine , medicine , nephritis , immunology , monocyte , ccl17 , endocrinology , antagonist , chemokine receptor , inflammation , receptor , disease
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.