Antagonist of monocyte chemoattractant protein 1 ameliorates the initiation and progression of lupus nephritis and renal vasculitis in MRL/lpr mice

Arthritis Rheum. 2003 Sep;48(9):2555-66. doi: 10.1002/art.11231.


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-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Antinuclear / blood
  • Chemokine CCL17
  • Chemokine CCL2 / antagonists & inhibitors*
  • Chemokine CCL2 / genetics
  • Chemokines, CC / antagonists & inhibitors
  • Chemokines, CC / genetics
  • Disease Progression
  • Gene Expression
  • Humans
  • Interferon-gamma / genetics
  • Interleukin-2 / genetics
  • K562 Cells
  • Kidney / blood supply
  • Kidney / pathology
  • Kidney / physiology
  • Lupus Nephritis / immunology*
  • Lupus Nephritis / pathology
  • Lupus Nephritis / therapy*
  • Mice
  • Mice, Inbred MRL lpr
  • Spleen / cytology
  • Transfection
  • Transplants
  • Vasculitis / immunology*
  • Vasculitis / pathology
  • Vasculitis / therapy*


  • Antibodies, Antinuclear
  • CCL17 protein, human
  • Ccl17 protein, mouse
  • Chemokine CCL17
  • Chemokine CCL2
  • Chemokines, CC
  • Interleukin-2
  • Interferon-gamma