Simvastatin decreases IL-6 and IL-8 production in epithelial cells
Simvastatin decreases IL-6 and IL-8 production in epithelial cells
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DOI：
10.1177/154405910608500608
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发表时间：
2006-06-01
影响因子：
7.6
通讯作者：
Izumi, Y.
中科院分区：
文献类型：
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作者：
Sakoda, K.;Yamamoto, M.;Izumi, Y.
许多心血管研究表明，3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂（他汀类药物）具有独立于降胆固醇的抗炎作用。作为一种慢性炎症性疾病，牙周炎与动脉粥样硬化有着共同的机制。由于口腔上皮细胞在牙周炎症中起着重要的作用，我们通过培养的人上皮细胞系（KB细胞）检测了辛伐他汀对白细胞介素-1 α产生的白细胞介素-6和白细胞介素-8的影响。辛伐他汀降低了产量，添加甲羟戊酸盐或焦磷酸香叶基香叶基而不是焦磷酸法尼酯可以逆转这一效应。辛伐他汀可降低KB细胞NF-kappa B和AP-1启动子活性。显性阴性的Rac1严重抑制白细胞介素-1 α诱导的nf - κ B和AP-1启动子活性。我们的结果可能表明辛伐他汀对人口腔上皮细胞具有抗炎作用，显然涉及抑制Rac1 GTPase。
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-1 alpha. Simvastatin decreased production, an effect reversed by adding mevalonate or geranylgeranyl pyrophosphate, but not farnesyl pyrophosphate. Simvastatin was found to reduce NF-kappa B and AP-1 promoter activity in KB cells. Dominant-negative Rac1 severely inhibited interleukin-1 alpha-induced NF-kappa B 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.