The Biotherapy Center, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China.
Department of Operative Dentistry and Endodontics, Guanghua School and Hospital of Stomatology, Sun Yat-sen University, Guangzhou, PR China.
Immunopharmacol Immunotoxicol. 2020 Oct;42(5):473-483. doi: 10.1080/08923973.2020.1810271. Epub 2020 Sep 4.
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.
Some C57BL/6 mice were administered ConA at a dose of 20 mg/kg (model mice), and some received 5 µg of Areg (treated mice). Then, their survival rates over 36 h were analyzed. After 5 h 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 .
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.
Areg showed direct protective effects against ConA-induced acute liver injury, which suggests the potential therapeutic application of Areg in immune-mediated ALF.
Amphiregulin（Areg）是表皮生长因子受体（EGFR）配体家族的一种糖蛋白，其在对抗组织损伤方面具有明确的保护作用；然而，其对免疫介导的肝损伤的影响尚不清楚。在这里，我们使用刀豆蛋白 A（ConA）诱导的急性肝炎模型来探讨 Areg 对免疫介导的急性肝损伤的影响。
将一些 C57BL/6 小鼠用 20mg/kg 的 ConA（模型小鼠）处理，一些用 5μg 的 Areg（处理小鼠）处理。然后，分析它们在 36 小时内的存活率。在治疗 5 小时后，研究了肝功能、肝组织学和肝组织细胞凋亡情况，并检测了细胞因子表达、中性粒细胞浸润和肝内活性。此外，还评估了没有 IL-22 时 Areg 的保护作用。
我们的结果表明，Areg 给药增加了急性肝衰竭（ALF）小鼠的存活率，恢复了肝功能，减轻了肝损伤。有趣的是，Areg 给药增加了肝组织 T 细胞中 IL-22 的产生，并上调了血清和肝脏中 IL-22 的浓度，而 IL-22 中和完全消除了 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。
Areg 对 ConA 诱导的急性肝损伤具有直接的保护作用，这表明 Areg 在免疫介导的 ALF 中具有潜在的治疗应用。
