Research Article
Antagonist of monocyte chemoattractant protein 1 ameliorates the initiation and progression of lupus nephritis and renal vasculitis in MRL/lpr mice
Hitoshi Hasegawa,
Masashi Kohno,
Miho Sasaki, Atsushi Inoue,
Mitsuko R. Ito,
Miho Terada, Kunio Hieshima,
Hiroki Maruyama,
Jun-ichi Miyazaki,
Osamu Yoshie, Masato Nose, Shigeru Fujita,
Corresponding Author
Hitoshi Hasegawa
Ehime University School of Medicine, Ehime, Japan
First Department of Internal Medicine, Ehime University School of Medicine, Shigenobu, Ehime 791-0295, JapanSearch for more papers by this authorMasashi Kohno
Ehime University School of Medicine, Ehime, Japan
Search for more papers by this authorAtsushi Inoue
Ehime University School of Medicine, Ehime, Japan
Search for more papers by this authorMitsuko R. Ito
Ehime University School of Medicine, Ehime, Japan
Search for more papers by this authorKunio Hieshima
Kinki University School of Medicine, Osaka, Japan
Search for more papers by this authorHiroki Maruyama
Niigata University School of Medicine, Niigata, Japan
Search for more papers by this authorJun-ichi Miyazaki
Osaka University Medical School, Osaka, Japan
Search for more papers by this authorShigeru Fujita
Ehime University School of Medicine, Ehime, Japan
Search for more papers by this authorHitoshi Hasegawa,
Masashi Kohno,
Miho Sasaki, Atsushi Inoue,
Mitsuko R. Ito,
Miho Terada, Kunio Hieshima,
Hiroki Maruyama,
Jun-ichi Miyazaki,
Osamu Yoshie, Masato Nose, Shigeru Fujita,
Corresponding Author
Hitoshi Hasegawa
Ehime University School of Medicine, Ehime, Japan
First Department of Internal Medicine, Ehime University School of Medicine, Shigenobu, Ehime 791-0295, JapanSearch for more papers by this authorMasashi Kohno
Ehime University School of Medicine, Ehime, Japan
Search for more papers by this authorAtsushi Inoue
Ehime University School of Medicine, Ehime, Japan
Search for more papers by this authorMitsuko R. Ito
Ehime University School of Medicine, Ehime, Japan
Search for more papers by this authorKunio Hieshima
Kinki University School of Medicine, Osaka, Japan
Search for more papers by this authorHiroki Maruyama
Niigata University School of Medicine, Niigata, Japan
Search for more papers by this authorJun-ichi Miyazaki
Osaka University Medical School, Osaka, Japan
Search for more papers by this authorShigeru Fujita
Ehime University School of Medicine, Ehime, Japan
Search for more papers by this authorAbstract
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-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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