Simvastatin decreases IL-6 and IL-8 production in epithelial cells.
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.
Sakoda
K
K
Department of Periodontology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Sakuragaoka 8-35-1, Kagoshima 890-8544, Japan. kenijis@denta.hal.kagoshima-u.ac.jp
Yamamoto
M
M
Negishi
Y
Y
Liao
J K
JK
Node
K
K
Izumi
Y
Y
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects; D005881:Gingiva / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000037:antagonists & inhibitors*; D007624:KB Cells; D008798:Mevalonic Acid / Q000494:pharmacology; D016328:NF-kappa B / Q000187:drug effects; D011106:Polyisoprenyl Phosphates / Q000494:pharmacology; D012717:Sesquiterpenes; D019821:Simvastatin / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000187:drug effects; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000093242:Interleukin-6 Inhibitors
D000893:Anti-Inflammatory Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D007375:Interleukin-1; D016209:Interleukin-8; D008798:Mevalonic Acid; D016328:NF-kappa B; D011106:Polyisoprenyl Phosphates; D012717:Sesquiterpenes; D019821:Simvastatin; D018808:Transcription Factor AP-1; D020741:rho GTP-Binding Proteins; D000093242:Interleukin-6 Inhibitors; C004808:farnesyl pyrophosphate; C002963:geranylgeranyl pyrophosphate