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

Research output: Contribution to journalArticlepeer-review

138 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2555-2566
Number of pages12
JournalArthritis and Rheumatism
Volume48
Issue number9
DOIs
Publication statusPublished - 2003 Sep 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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