MCP-1 induces activation of MAP-kinases ERK, JNK and p38 MAPK in human endothelial cells

Cardiovasc Res. 2002 Nov;56(2):284-92. doi: 10.1016/s0008-6363(02)00600-4.


Activation of vascular endothelial cells (ECs) plays an important pathogenic role in the development of atherosclerosis. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemoattractant of monocytes. Besides induction of monocyte recruitment, it has been suggested that MCP-1 can also affect the cellular responses of ECs. We investigated whether MCP-1 activated the three major mitogen activated protein (MAP)-kinases extracellular signal-regulated kinase (ERK), c-Jun amino terminal kinase (JNK) and p38 MAPK. Stimulation of ECs with MCP-1 induced a time- and concentration-dependent activation of all three MAP-kinases, concentrations as low as 0.1 ng/ml were sufficient for this mechanism. MCP-1 also induced secretion of matrix metalloproteinase (MMP)-2 which along with ERK activation was inhibited by PD098059. The results demonstrate that MCP-1 can lead to direct activation of MAP kinases together with induction of MMP2 in ECs. Our data thus propose a new mechanism for the proatherogenic effect of MCP-1.

MeSH terms

  • Cell Culture Techniques
  • Chemokine CCL2 / pharmacology*
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / enzymology*
  • Gene Expression
  • Humans
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases / metabolism*
  • Phosphorylation
  • RNA, Messenger / genetics
  • Receptors, CCR2
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / metabolism
  • Signal Transduction
  • p38 Mitogen-Activated Protein Kinases


  • CCR2 protein, human
  • Chemokine CCL2
  • RNA, Messenger
  • Receptors, CCR2
  • Receptors, Chemokine
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases