Targeting Monocyte Chemoattractant protein-1 Signalling in Disease

Expert Opin Ther Targets. 2003 Feb;7(1):35-48. doi: 10.1517/14728222.7.1.35.

Abstract

Monocyte chemoattractant protein-1 (MCP-1) has been implicated in many inflammatory and autoimmune diseases. The G-protein-coupled receptor CCR-2B is probably the most important MCP-1 receptor in vivo, and loss of MCP-1 effector function alone is sufficient to impair monocytic trafficking in inflammation models. MCP-1 signalling appears to be a relevant target, especially in rheumatoid arthritis (RA). In RA patients, MCP-1 is produced by synovial cells and infiltrating monocytes, plasma MCP-1 concentrations correlate with swollen joint count, and elevated serum MCP-1 concentrations were found in juvenile RA in patients with active disease. Modulation of MCP-1 signalling in experimental RA showed beneficial effects on inflammation and joint destruction. With respect to chronic neuroinflammation, a critical role for MCP-1 has been established in animal models for multiple sclerosis. In acute neuroinflammation, experimental evidence for a detrimental role of MCP-1 in stroke and excitotoxic injury has been found. Several selective small molecular weight CCR-2B antagonists and MCP-1-blocking antibodies have been described. The proof for the validity of targeting MCP-1 signalling in disease, however, has yet to be established in clinical trials.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Antirheumatic Agents / pharmacology
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / physiopathology
  • Central Nervous System / drug effects
  • Central Nervous System / injuries
  • Chemokine CCL2 / antagonists & inhibitors*
  • Chemokine CCL2 / deficiency
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / physiology
  • Drug Design*
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy
  • Humans
  • Inflammation / drug therapy
  • Mice
  • Mice, Inbred MRL lpr
  • Mice, Knockout
  • Models, Molecular
  • Molecular Structure
  • Multiple Sclerosis / drug therapy
  • Obesity / drug therapy
  • Receptors, CCR2
  • Receptors, Chemokine / antagonists & inhibitors
  • Receptors, Chemokine / deficiency
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / physiology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology

Substances

  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal
  • Antirheumatic Agents
  • CCL2 protein, human
  • CCR2 protein, human
  • Ccl2 protein, mouse
  • Ccr2 protein, mouse
  • Chemokine CCL2
  • Receptors, CCR2
  • Receptors, Chemokine