Objectives Amphiregulin (Areg), a glycoprotein from the epidermal growth factor receptor (EGFR) ligand family, has a well-documented protective role against tissue injury; however, its effects on immune-mediated liver injury are still unclear. Here, we used a concanavalin A (ConA)-induced acute liver hepatitis model to explore the effects of Areg on immune-mediated acute liver injury.

Materials and methods Some C57BL/6 mice were administered ConA at a dose of 20 mg/kg (model mice), and some received 5µg of Areg (treated mice). Then,their survival rates over 36 hours were analysed. After 5 hours of treatment, liver function, hepatic histology and apoptosis in liver tissue were investigated, and cytokine expression and neutrophil infiltration and activity in the liver were detected. Moreover, the protective effects of Areg were also evaluated without IL-22 in vivo.

Results Our results showed that Areg administration increased acute liver failure (ALF) mouse survival, restored liver function and alleviated liver damage. Interestingly, Areg administration increased IL-22 production in hepatic T cells and upregulated IL-22 concentrations in the serum and liver, whereas IL-22 neutralization completely abolished the therapeutic effect of Areg. Meanwhile, Areg administration was concomitant with increased expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL, which are important in the hepatoprotective mechanism of IL-22.

Conclusion Areg showed direct protective effects against ConA-induced acute liver injury, which suggests the potential therapeutic application of Areg in immune-mediated ALF.

目的两性调节蛋白（Areg）是一种来自表皮生长因子受体（EGFR）配体家族的糖蛋白，对组织损伤具有保护作用。然而，其对免疫介导的肝损伤的作用仍不清楚。在这里，我们使用伴刀豆球蛋白A（ConA）诱导的急性肝炎肝炎模型来探讨Areg对免疫介导的急性肝损伤的影响。

材料和方法一些C57BL / 6小鼠以20 mg / kg的剂量施用ConA（模型小鼠），而另一些小鼠则接受了5μg的Areg（治疗的小鼠）。然后，分析了他们在36小时内的生存率。治疗5小时后，调查肝组织的肝功能，肝组织学和凋亡，并检测肝中细胞因子的表达和中性粒细胞的浸润及活性。此外，还评估了在没有IL-22的情况下Areg的保护作用。

结果我们的结果表明，Areg给药可提高小鼠急性肝衰竭（ALF）存活率，恢复肝功能并减轻肝损伤。有趣的是，Areg给药可增加肝T细胞中IL-22的产生，并上调血清和肝脏中IL-22的浓度，而IL-22中和作用则完全废除了Areg的治疗作用。同时，Areg给药伴随着抗凋亡蛋白Bcl-2和Bcl-xL的表达增加，这在IL-22的肝保护机制中很重要。

结论Areg对ConA引起的急性肝损伤具有直接的保护作用，表明Areg在免疫介导的ALF中具有潜在的治疗应用。