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

Su Yung Kim, Carlos Guijarro, Michael P. O'Donnell, Bertram L. Kasiske, Youngki Kim, William F. Keane

Research output: Contribution to journalArticle

78 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)363-371
Number of pages9
JournalKidney international
Volume48
Issue number2
DOIs
StatePublished - Aug 1995

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    Kim, S. Y., Guijarro, C., O'Donnell, M. P., Kasiske, B. L., Kim, Y., & Keane, W. F. (1995). Human mesangial cell production of monocyte chemoattractant protein-1: Modulation by lovastatin. Kidney international, 48(2), 363-371. https://doi.org/10.1038/ki.1995.304