Abstract
Many cardiovascular studies have suggested that 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors (statins) have anti-inflammatory effects independent of cholesterol lowering. As a chronic inflammatory disease, periodontitis shares some mechanisms with atherosclerosis. Since oral epithelial cells participate importantly in periodontal inflammation, we measured simvastatin effects on interleukin-6 and interleukin-8 production by cultured human epithelial cell line (KB cells) in response to interleukin-1alpha. Simvastatin decreased production, an effect reversed by adding mevalonate or geranylgeranyl pyrophosphate, but not farnesyl pyrophosphate. Simvastatin was found to reduce NF-kappaB and AP-1 promoter activity in KB cells. Dominant-negative Rac1 severely inhibited interleukin-1alpha-induced NF-kappaB and AP-1 promoter activity. Our results may indicate an anti-inflammatory effect of simvastatin on human oral epithelial cells, apparently involving Rac1 GTPase inhibition.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Inflammatory Agents / pharmacology*
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Epithelial Cells / drug effects
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Gingiva / cytology
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Gingiva / drug effects*
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Humans
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
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Hypolipidemic Agents / pharmacology*
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Interleukin-1 / pharmacology
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Interleukin-6 / antagonists & inhibitors*
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Interleukin-8 / antagonists & inhibitors*
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KB Cells
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Mevalonic Acid / pharmacology
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NF-kappa B / drug effects
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Polyisoprenyl Phosphates / pharmacology
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Sesquiterpenes
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Simvastatin / pharmacology*
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Transcription Factor AP-1 / drug effects
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rho GTP-Binding Proteins / antagonists & inhibitors
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rho GTP-Binding Proteins / pharmacology
Substances
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Anti-Inflammatory Agents
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Hydroxymethylglutaryl-CoA Reductase Inhibitors
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Hypolipidemic Agents
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Interleukin-1
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Interleukin-6
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Interleukin-8
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NF-kappa B
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Polyisoprenyl Phosphates
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Sesquiterpenes
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Transcription Factor AP-1
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farnesyl pyrophosphate
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Simvastatin
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rho GTP-Binding Proteins
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geranylgeranyl pyrophosphate
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Mevalonic Acid