Inhibitory effect of statins on inflammatory cytokine production from human bronchial epithelial cells

被引：71

作者：

Iwata, A. ^{[1
]}

Shirai, R. ^{[1
]}

Ishii, H. ^{[1
]}

Kushima, H. ^{[1
]}

Otani, S. ^{[1
]}

Hashinaga, K. ^{[1
]}

Umeki, K. ^{[1
]}

Kishi, K. ^{[1
]}

Tokimatsu, I. ^{[1
]}

Hiramatsu, K. ^{[1
]}

Kadota, J. ^{[1
]}

机构：

[1] Oita Univ, Fac Med, Yufu City, Oita 8795593, Japan

来源：

CLINICAL AND EXPERIMENTAL IMMUNOLOGY | 2012年 / 168卷 / 02期

关键词：

bronchial epithelial cell; inflammatory cytokine; mevaloate; RhoA; statin; ENDOTHELIAL FUNCTION; IN-VITRO; PNEUMONIA; ATORVASTATIN; MORTALITY; THERAPY; MARKERS; OUTCOMES; RELEASE; SEPSIS;

D O I：

10.1111/j.1365-2249.2012.04564.x

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：234 / 240

页数：7

共 33 条

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