Document Detail

Low-density lipoprotein-induced expression of interleukin-6, a marker of human mesangial cell inflammation: effects of oxidation and modulation by lovastatin.
MedLine Citation:
PMID:  10631097     Owner:  NLM     Status:  MEDLINE    
Low-density lipoprotein (LDL) may contribute to the pathogenesis of glomerulosclerosis by stimulating a mesangial cell inflammatory response. Interleukin-6 (IL-6) is a marker of active inflammation and ongoing glomerular injury. Therefore, we investigated the effects of native and oxidized LDL on human mesangial cell production of IL-6 and a possible modulation of this inflammatory response by lovastatin, which has been shown to ameliorate experimental glomerulosclerosis. Human mesangial cells were exposed for 6 or 24 h to culture medium containing either native LDL alone or a LDL mixture containing 5 or 20% oxidized LDL. We found that native LDL stimulated 6 h mRNA expression and secretion of IL-6. This effect was further enhanced, in a dose-related manner, when mesangial cells were exposed to increasing concentrations of oxidized LDL. Lovastatin markedly inhibited mesangial cell expression of IL-6 mRNA and reduced IL-6 secretion. The inhibitory effects of lovastatin were overridden at least partially by exogenous mevalonate. We conclude that LDL, and particularly oxidized LDL, might contribute to the pathogenesis of glomerular disease by modulating the inflammatory response of human mesangial cells, as assessed by the stimulation of IL-6 expression. Moreover, this inflammatory response can be prevented by lovastatin, providing a potential direct anti-inflammatory mechanism by which HMG-CoA reductase inhibitors may attenuate lipid-induced glomerular injury.
Z A Massy; Y Kim; C Guijarro; B L Kasiske; W F Keane; M P O'Donnell
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  267     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2000 Jan 
Date Detail:
Created Date:  2000-02-23     Completed Date:  2000-02-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  536-40     Citation Subset:  IM    
Copyright Information:
Copyright 2000 Academic Press.
Division of Nephrology, Department of Medicine, Hennepin County Medical Center, Minneapolis, Minnesota, USA.
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MeSH Terms
Base Sequence
Biological Markers
Cells, Cultured
DNA Primers / genetics
Glomerular Mesangium / cytology,  drug effects*,  metabolism*
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
Inflammation Mediators / metabolism
Interleukin-6 / biosynthesis*,  genetics*
Lipoproteins, LDL / pharmacology*
Lovastatin / pharmacology*
Reg. No./Substance:
0/Biological Markers; 0/DNA Primers; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Inflammation Mediators; 0/Interleukin-6; 0/Lipoproteins, LDL; 0/oxidized low density lipoprotein; 75330-75-5/Lovastatin

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