IL-6 Trans-Signaling Plays Important Protective Roles in Acute Liver Injury Induced by Acetaminophen in Mice
IL-6 Trans-Signaling Plays Important Protective Roles in Acute Liver Injury Induced by Acetaminophen in Mice
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IL-6 反式信号在对乙酰氨基酚诱导的小鼠急性肝损伤中发挥重要保护作用
DOI：
10.1002/jbt.21708
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发表时间：
2015-06-01
影响因子：
3.6
通讯作者：
Meng, Hong-Ye
中科院分区：
文献类型：
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作者：
Li, San-Qiang;Zhu, Sha;Meng, Hong-Ye
本研究旨在探讨白细胞介素-6（IL-6）反式信号转导在醋氨酚（AAP）肝损伤中的重要作用。可溶性gp 130蛋白（sgp 130 Fc）专门抑制IL-6反式信号传导，而IL-6/可溶性IL-6受体（sIL-6 R）融合蛋白（hyper-IL-6）模拟IL-6反式信号传导。利用这些工具，我们研究了IL-6反式信号转导在AAP诱导的肝损伤中的作用。阻断AAP诱导的肝损伤过程中IL-6反式信号通路可显著升高血清谷草转氨酶和谷丙转氨酶水平，降低血清sIL-6 R水平，加重肝损伤，抑制磷酸化STAT 3（pSTAT 3）、增殖细胞核抗原（PCNA）、血管内皮生长因子（VEGF）的表达和糖原合成。诱导小鼠肝细胞Caspase 3、细胞色素P450 2 E1（CYP 2 E1）表达及肝细胞凋亡。综上所述，我们的研究表明，IL-6反式信号转导在AAP诱导的小鼠肝损伤中通过调节肝细胞增殖和凋亡、血管生成、CYP 2 E1表达和糖原代谢发挥重要的保护作用。(C)2015 Wiley Periodicals，Inc.
Our study was undertaken to evaluate the important role of interleukin-6 (IL-6) trans-signaling in acetaminophen (AAP)-induced liver injury. A soluble gp130 protein (sgp130Fc) exclusively inhibits IL-6 trans-signaling, whereas an IL-6/soluble IL-6 receptor (sIL-6R) fusion protein (hyper-IL-6) mimics IL-6 trans-signaling. Using these tools, we investigated the role of IL-6 trans-signaling in AAP-induced liver injury. Blockade of IL-6 trans-signaling during AAP-induced liver injury remarkably increased the levels of serum aspartate aminotransferase and alanine aminotransferase; lowered the level of serum sIL-6R; aggravated liver injury; inhibited the expression of phosphorylation of STAT3 (pSTAT3), proliferating cell nuclear antigen, vascular endothelial growth factor, and glycogen synthesis; and induced the expression of Caspase3, cytochrome P450 2E1 (CYP2E1), and hepatocyte apoptosis in the liver of mice. In summary, our study suggested that IL-6 trans-signaling plays important protective roles by regulating the hepatocyte proliferation and apoptosis, angiogenesis, CYP2E1 expression, and glycogen metabolism during AAP-induced liver injury in mice. (C) 2015 Wiley Periodicals, Inc.