PMID- 12556201
OWN - NLM
STAT- MEDLINE
DCOM- 20060501
LR  - 20220408
IS  - 1744-7631 (Electronic)
IS  - 1472-8222 (Linking)
VI  - 7
IP  - 1
DP  - 2003 Feb
TI  - Targeting monocyte chemoattractant protein-1 signalling in disease.
PG  - 35-48
AB  - 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.
FAU - Dawson, Janet
AU  - Dawson J
AD  - Arthritis and Bone Metabolism Research, Novartis Pharma AG, Basel, Switzerland.
FAU - Miltz, Wolfgang
AU  - Miltz W
FAU - Mir, Anis K
AU  - Mir AK
FAU - Wiessner, Christoph
AU  - Wiessner C
LA  - eng
PT  - Journal Article
PT  - Review
PL  - England
TA  - Expert Opin Ther Targets
JT  - Expert opinion on therapeutic targets
JID - 101127833
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antirheumatic Agents)
RN  - 0 (CCL2 protein, human)
RN  - 0 (CCR2 protein, human)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
SB  - IM
MH  - Alzheimer Disease/drug therapy
MH  - Animals
MH  - Anti-Inflammatory Agents/pharmacology/therapeutic use
MH  - Antibodies, Monoclonal/pharmacology/therapeutic use
MH  - Antirheumatic Agents/pharmacology/therapeutic use
MH  - Arthritis, Rheumatoid/drug therapy/physiopathology
MH  - Central Nervous System/drug effects/injuries
MH  - Chemokine CCL2/*antagonists & inhibitors/deficiency/genetics/physiology
MH  - *Drug Design
MH  - Encephalomyelitis, Autoimmune, Experimental/drug therapy
MH  - Humans
MH  - Inflammation/drug therapy
MH  - Mice
MH  - Mice, Inbred MRL lpr
MH  - Mice, Knockout
MH  - Models, Molecular
MH  - Molecular Structure
MH  - Multiple Sclerosis/drug therapy
MH  - Obesity/drug therapy
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/antagonists & inhibitors/deficiency/genetics/physiology
MH  - Signal Transduction/drug effects/physiology
RF  - 137
EDAT- 2003/01/31 04:00
MHDA- 2006/05/02 09:00
CRDT- 2003/01/31 04:00
PHST- 2003/01/31 04:00 [pubmed]
PHST- 2006/05/02 09:00 [medline]
PHST- 2003/01/31 04:00 [entrez]
AID - 10.1517/14728222.7.1.35 [doi]
PST - ppublish
SO  - Expert Opin Ther Targets. 2003 Feb;7(1):35-48. doi: 10.1517/14728222.7.1.35.