Human mesangial cell production of monocyte chemoattractant protein-1: modulation by lovastatin

Kidney Int. 1995 Aug;48(2):363-71. doi: 10.1038/ki.1995.304.


Macrophages play a critical role in the progression of clinical and experimental glomerular injury. Serum-stimulated human fetal mesangial cells in culture produce a chemotactic factor that is monocyte-selective. This chemotactic factor is most likely monocyte chemoattractant protein-1 (MCP-1) as a monoclonal antibody directed against MCP-1, but not an irrelevant antibody, suppressed the mesangial cell-derived chemotactic activity. Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase by lovastatin resulted in a reduction of the mesangial cell-derived chemotactic activity as well as MCP-1 mRNA expression. The inhibitory effects of lovastatin in the presence of exogenous cholesterol were reversed by mevalonate, suggesting a role for isoprenoid intermediates of the mevalonate pathway and/or isoprenylated proteins in mesangial cell MCP-1 regulation. These findings suggest an additional mechanism by which HMG-CoA reductase inhibition in vivo may reduce glomerular injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Chemokine CCL2 / biosynthesis*
  • Chemokine CCL2 / genetics
  • Glomerular Mesangium / cytology
  • Glomerular Mesangium / metabolism*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lovastatin / pharmacology*
  • RNA, Messenger / antagonists & inhibitors
  • RNA, Messenger / metabolism
  • Time Factors


  • Chemokine CCL2
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • RNA, Messenger
  • Lovastatin