title: Human mesangial cell production of monocyte chemoattractant protein-1: modulation by lovastatin.
abstract: 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.
authors.affiliation: Department of Medicine, Hennepin County Medical Center, Minneapolis, Minnesota, USA.
authors.forename: S Y
authors.initials: SY
authors.lastname: Kim
authors.forename: C
authors.initials: C
authors.lastname: Guijarro
authors.forename: M P
authors.initials: MP
authors.lastname: O'Donnell
authors.forename: B L
authors.initials: BL
authors.lastname: Kasiske
authors.forename: Y
authors.initials: Y
authors.lastname: Kim
authors.forename: W F
authors.initials: WF
authors.lastname: Keane
mesh_terms: D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors
chemical_list: D018932:Chemokine CCL2; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012333:RNA, Messenger; D008148:Lovastatin