Internal Medicine II, Oita University Faculty of Medicine, Oita, Japan.
Clin Exp Immunol. 2012 May;168(2):234-40. doi: 10.1111/j.1365-2249.2012.04564.x.
Statins are 3-hydroxy-3-methylglutaryl-co-enzyme A reductase inhibitors of cholesterol biosynthesis, and have been reported to exert pleiotropic effects on cellular signalling and cellular functions involved in inflammation. Recent reports have demonstrated that previous statin therapy reduced the risk of pneumonia or increased survival in patients with community-acquired pneumonia. However, the precise mechanisms responsible for these effects are unclear. In the present study, we examined the effects of statins on cytokine production from lipopolysaccharide (LPS)-stimulated human bronchial epithelial cells (BEAS-2B). Interleukin (IL)-6 and IL-8 mRNA expression and protein secretion in LPS-stimulated cells were inhibited significantly by the lipophilic statin pitavastatin and the hydrophilic statin pravastatin. As these inhibitory effects of statin were negated by adding mevalonate, the anti-inflammatory effects of statins appear to be exerted via the mevalonic cascade. In addition, the activation levels of Ras homologue gene family A (RhoA) in BEAS-2B cells cultured with pitavastatin were significantly lower than those without the statin. These results suggest that statins have anti-inflammatory effects by reducing cytokine production through inhibition of the mevalonic cascade followed by RhoA activation in the lung.
他汀类药物是胆固醇生物合成的 3-羟基-3-甲基戊二酰辅酶 A 还原酶抑制剂，据报道它们对细胞信号转导和参与炎症的细胞功能具有多种作用。最近的报告表明，先前的他汀类药物治疗降低了社区获得性肺炎患者的肺炎风险或提高了生存率。然而，这些作用的确切机制尚不清楚。在本研究中，我们研究了他汀类药物对脂多糖（LPS）刺激的人支气管上皮细胞（BEAS-2B）产生细胞因子的影响。亲脂性他汀类药物匹伐他汀和亲水性他汀类药物普伐他汀显著抑制 LPS 刺激细胞中的白细胞介素（IL）-6 和 IL-8 mRNA 表达和蛋白分泌。由于添加甲羟戊酸可否定他汀类药物的这些抑制作用，因此他汀类药物的抗炎作用似乎是通过甲羟戊酸途径发挥的。此外，用匹伐他汀培养的 BEAS-2B 细胞中的 Ras 同源基因家族 A（RhoA）的激活水平明显低于没有他汀类药物的细胞。这些结果表明，他汀类药物通过抑制甲羟戊酸途径并随后抑制 RhoA 激活来减少细胞因子的产生，从而发挥抗炎作用。
