Homocysteine stimulates nuclear factor kappaB activity and monocyte chemoattractant protein-1 expression in vascular smooth-muscle cells: a possible role for protein kinase C

Biochem J. 2000 Dec 15;352 Pt 3(Pt 3):817-26.


Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that stimulates the migration of monocytes into the intima of arterial walls. Although many factors that induce MCP-1 expression have been identified, the effect of homocysteine on the expression of MCP-1 in atherogenesis and the underlying mechanisms are not entirely clear. The objective of the present study was to investigate the role of homocysteine in MCP-1 expression in human aorta vascular smooth-muscle cells (VSMCs). After VSMCs were incubated with homocysteine for various time periods, a nuclease protection assay and ELISA were performed. Homocysteine (0.05-0.2 mM) significantly increased the expression of MCP-1 mRNA (up to 2. 7-fold) and protein (up to 3.3-fold) in these cells. The increase in MCP-1 expression was associated with the activation of protein kinase C (PKC) as well as nuclear factor kappaB (NF-kappaB). Further investigation demonstrated that the activation of NF-kappaB was the result of a PKC-mediated reduction in the expression of inhibitory protein (IkappaBalpha) mRNA and protein in homocysteine-treated cells. Oxidative stress might also be involved in the activation of NF-kappaB by homocysteine in VSMCs. In conclusion, the present study has clearly demonstrated that the activation of PKC as well as superoxide production followed by activation of NF-kappaB is responsible for homocysteine-induced MCP-1 expression in VSMCs. These results suggest that homocysteine-stimulated MCP-1 expression via NF-kappaB activation may play an important role in atherogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Calcium / metabolism
  • Cell Line
  • Chemokine CCL2 / biosynthesis*
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • DNA / genetics
  • DNA / metabolism
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Enzyme Activation / drug effects
  • Enzyme-Linked Immunosorbent Assay
  • Homocysteine / pharmacology*
  • Humans
  • I-kappa B Proteins*
  • Models, Biological
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / enzymology
  • Muscle, Smooth, Vascular / metabolism
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Nuclease Protection Assays
  • Oxidative Stress / drug effects
  • Phosphoproteins / biosynthesis
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Protein Binding / drug effects
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism*
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Superoxide Dismutase / antagonists & inhibitors
  • Superoxide Dismutase / metabolism
  • Up-Regulation / drug effects


  • Chemokine CCL2
  • DNA-Binding Proteins
  • I-kappa B Proteins
  • NF-kappa B
  • NFKBIA protein, human
  • Phosphoproteins
  • RNA, Messenger
  • Homocysteine
  • NF-KappaB Inhibitor alpha
  • DNA
  • Superoxide Dismutase
  • Protein Kinase C
  • Calcium