ANTIOXIDATIVE ROLE OF INTERLEUKIN-6 IN SEPTIC LUNG INJURY IN MICE
ANTIOXIDATIVE ROLE OF INTERLEUKIN-6 IN SEPTIC LUNG INJURY IN MICE
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DOI：
10.1177/039463200802100303
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发表时间：
2008-07-01
影响因子：
3.5
通讯作者：
Yoshikawa, T.
中科院分区：
文献类型：
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作者：
Inoue, K.;Takano, H.;Yoshikawa, T.
我们以前已经证明了白细胞介素（IL）-6对脓毒性肺损伤的保护作用，由脂多糖（LPS）诱导使用IL-6基因敲除（-/-）小鼠。这种保护至少部分地通过抑制促炎细胞因子的增强的局部表达来介导。在本研究中，我们使用IL-6（-/-）和相应的野生型（WT）小鼠研究IL-6是否调节LPS暴露产生的肺中的氧化应激。腹腔内LPS（1 mg/kg）激发可诱导两种基因型小鼠肺中诱导型一氧化氮合酶和血红素加氧酶-1的转录表达。在LPS的存在下，这些表达在IL-6（-/-）中显著高于WT小鼠。免疫组织化学还显示，与载体相比，LPS诱导肺中8-羟基-2 '-脱氧鸟苷形成的显著增加。此外，在存在LPS攻击的情况下，IL-6（-/-）中的形成比WT小鼠中更强烈。在LPS存在下，IL-6（-/-）小鼠肺中的脂质过氧化作用显著高于WT小鼠。这些数据表明，可能的机制，其中内源性IL-6保护对脓毒性肺损伤诱导的LPS涉及，至少部分，其抗氧化特性。
We have previously demonstrated the protective role of interleukin (IL)-6 against septic lung injury induced by lipopolysaccharide (LPS) using IL-6 knock-out (-/-) mice. This protection is mediated, at least partly, through the inhibition of the enhanced local expression of proinflammatory cytokines. In the present study, we addressed whether IL-6 regulates oxidative stress in the lung generated by LPS exposure using IL-6 (-/-) and corresponding wild type (WT) mice. Intraperitoneal LPS (1 mg/kg) challenge induced transcriptional expressions of inducible nitric oxide synthase and heme oxygenase-1 in the lung of mice with both genotypes. In the presence of LPS, these expressions were significantly greater in IL-6 (-/-) than in WT mice. Immunohistochemistry also showed that LPS induced a significant increase in 8-hydroxy-2'-deoxyguanosine formation in the lung as compared to vehicle. Furthermore, the formation was more intense in IL-6 (-/-) than in WT mice in the presence of LPS challenge. In the presence of LPS, lipid peroxidation in the lung was significantly greater in IL-6 (-/-) than in WT mice. These data suggest that the possible mechanisms in which endogenous IL-6 protects against septic lung injury induced by LPS involve, at least in part, its antioxidative properties.