Preventive effects of interleukin-6 in lipopolysaccharide/D-galactosamine induced acute liver injury via regulating inflammatory response in hepatic macrophages
Preventive effects of interleukin-6 in lipopolysaccharide/D-galactosamine induced acute liver injury via regulating inflammatory response in hepatic macrophages
复制标题
白细胞介素6通过调节肝巨噬细胞炎症反应预防脂多糖/D-半乳糖胺诱导的急性肝损伤
DOI：
10.1016/j.intimp.2017.08.009
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发表时间：
2017-10-01
影响因子：
5.6
通讯作者：
Li, Xuejun
中科院分区：
文献类型：
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作者：
Li, Long;Duan, Chaoli;Li, Xuejun
脂多糖/D-氨基半乳糖(LPS/D-Gal)诱导的急性肝损伤以明显的炎症反应为特征，包括肿瘤坏死因子-α和白介素6，是一种广泛应用于炎症研究的实验模型。肿瘤坏死因子-α在内毒素/D-半乳糖诱导的肝损伤过程中起关键作用。然而，IL-6在该模型中的作用尚不清楚。本研究旨在阐明IL-6在脂多糖/D-半乳糖诱导的小鼠急性肝损伤发病机制中的作用。给C57BL/6小鼠腹腔注射脂多糖(50微克/千克体重)和D-半乳糖(400毫克/千克体重)造成急性肝损伤。在注射脂多糖/D-半乳糖前2小时，注射生理盐水或单次注射重组IL-6(200微克/公斤体重)。分别于注射内毒素/D-半乳糖后2 h和6 h处死小鼠。结果表明，IL-6对脂多糖/D-半乳糖诱导的小鼠肝组织损伤、丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)升高以及肝细胞凋亡和炎症均有保护作用。此外，体外研究表明，IL-6可显著抑制内毒素诱导的巨噬细胞促炎细胞因子和趋化因子、肿瘤坏死因子-α、RANTES和单核细胞趋化蛋白-1的表达，而促进巨噬细胞M2标志Arg-1和MRC-1的表达。综上所述，这些发现揭示了IL-6通过调节肝巨噬细胞的炎症反应而在改善内毒素/D-半乳糖诱导的急性肝损伤中的新的和意想不到的作用。
Lipopolysaccharide/D-Galactosamine (LPS/D-Gal)-induced acute liver injury is characterized by significant inflammatory responses including TNF-alpha and interleukin-6 (IL-6) and is a widely applied experimental model for inflammation research. TNF-alpha is critical in the progression of LPS/D-Gal-induced liver injury. However, the role of IL-6 in this model is still unknown. In the present study, we aim to elucidate the involvement of IL-6 in the pathogenesis of acute liver injury induced by LPS/D-Gal in mice and its underlying mechanism. To induce acute liver injury, LPS (50 mu g/kg body weight) and D-Gal (400 mg/kg body weight) were injected intraperitoneally in the C57BL/6 mice. The vehicle (saline) or a single dose of recombinant IL-6 (200 mu g/kg body weight) was administered 2 h prior to LPS/D-Gal injection. Mice were sacrificed 2 h and 6 h after LPS/D-Gal injection. The results indicated that IL-6 treatment could protect mice from LPS/D-Gal-induced tissue damage, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation, as well as hepatocyte apoptosis and inflammation. Furthermore, in vitro study showed that IL-6 treatment could significantly suppress LPS-triggered expression of proinflammatory cytokines and chemokines, TNF-alpha, RANTES and MCP-1 in macrophages while promoting the expression of M2 markers, such as Arg-1 and Mrc-1 in macrophages. Taken together, these findings revealed a novel and unexpected role of IL-6 in ameliorating LPS/D-Gal-induced acute liver injury via regulating inflammatory responses in hepatic macrophages.