Role of interleukin-6 in hepatic heat shock protein expression and protection against acetaminophen-induced liver disease
Role of interleukin-6 in hepatic heat shock protein expression and protection against acetaminophen-induced liver disease
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DOI：
10.1016/s0006-291x(03)00572-2
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发表时间：
2003-04-25
影响因子：
3.1
通讯作者：
Pohl, LR
中科院分区：
文献类型：
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作者：
Masubachi, Y;Bourdi, M;Pohl, LR
最近的实验数据表明，药物性肝病（DILD）的特殊性可能部分归因于一种或多种肝脏保护因子的缺乏。在这项研究中，我们调查了白细胞介素（IL）-6是否也可能是这些因素之一。在用对乙酰氨基酚（APAP）诱导肝损伤后，在野生型（WT）小鼠中观察到IL-6及其家族成员IL-11、白血病抑制因子和制瘤素M的肝mRNA表达的时间依赖性增加，这表明该细胞因子家族可能发挥肝保护作用。事实上，缺乏IL-6（IL-6（-/-））的小鼠比WT小鼠更容易受到APAP诱导的肝损伤。IL-6（-/-）小鼠的易感性增加与APAP治疗后肝热休克蛋白（HSP）25、32和40以及诱导型HSP 70表达不足有关。这些结果表明，IL-6和其他可能的家庭成员可能保护肝脏免受损伤，至少在部分，通过上调几个细胞保护热休克蛋白的肝表达。(C)2003 Elsevier Science（美国）。All rights reserved.
Recent experimental data suggest that the idiosyncratic nature of drug-induced liver disease (DILD) may be due in part to a deficiency of one or more hepatoprotective factors. In this study we have investigated whether interleukin (IL)-6 may also be one of these factors. Following the induction of liver injury with acetaminophen (APAP), a time-dependent increase in liver mRNA expression of IL-6 and its family members IL-11, leukemia inhibitory factor, and oncostatin M was observed in wild type (WT) mice, suggesting a possible hepatoprotective role played by this cytokine family. Indeed, mice lacking IL-6 (IL-6(-/-)) were more susceptible than were WT mice to APAP-induced liver injury. The increased susceptibility of the IL-6(-/-) mice was associated with a deficiency in the expression of hepatic heat shock protein (HSP)25, 32, and 40 as well as inducible HSP70 following APAP treatment. These results suggest that IL-6 and possibly other family members may protect the liver from injury, at least in part, by up-regulating the hepatic expression of several cytoprotective HSPs. (C) 2003 Elsevier Science (USA). All rights reserved.