Simvastatin decreases IL-6 and IL-8 production in epithelial cells |
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Authors: | Sakoda K Yamamoto M Negishi Y Liao J K Node K Izumi Y |
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Affiliation: | 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 |
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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. |
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