Department of Biochemistry, Molecular Cancer Research Center, School of Medicine, Sun Yat-sen University, Shenzhen 518107, Guangdong Province, China.
Department of Biochemistry, Molecular Cancer Research Center, School of Medicine, Sun Yat-sen University, Shenzhen 518107, Guangdong Province, China; Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China.
Cytokine. 2022 Oct;158:155979. doi: 10.1016/j.cyto.2022.155979. Epub 2022 Jul 29.
Cholestasis caused by bile secretion and excretion disorders is a serious manifestation of hepatopathy. Interleukin (IL)-25 is a member of the IL-17 cytokine family, which involves in mucosal immunity and type 2 immunity via its receptor-IL-17RB. Our previous studies have shown that IL-25 improves non-alcoholic fatty liver via stimulating M2 macrophage polarization and promotes development of hepatocellular carcinoma via alternative activation of macrophages. These hepatopathy are closely associated with cholestasis. However, whether IL-25 play an important role in cholestasis remains unclear. IL-25 treatment and IL-25 knockout (Il25) mice were injected intragastrically with α-naphthyl isothiocyanate (ANIT) to determine the biological association between IL-25 and cholestasis. Here, we found that IL-25 and IL-17RB decreased in ANIT-induced cholestatic mice. Il25 mice showed exacerbated ANIT-induced parenchymal injury and IL-25 treatment significantly alleviated cholestatic liver injury induced by ANIT. We found that IL-25 reduced the level of hepatic total bile acids and increased the expression of multidrug resistance-associated protein 2 (MRP2) and multidrug resistance-associated protein 3 (MRP3) in liver. In conclusion, IL-25 exhibited a protective effect against ANIT-induced cholestatic liver injury in mice, which may be related to the regulation on bile acids secretion. These results provide a theoretical basis for the use of IL-25 in the treatment of cholestatic hepatopathy.
胆汁分泌和排泄障碍引起的胆汁淤积是肝病的严重表现。白细胞介素 (IL)-25 是 IL-17 细胞因子家族的一员，通过其受体-IL-17RB 参与黏膜免疫和 2 型免疫。我们之前的研究表明，IL-25 通过刺激 M2 巨噬细胞极化改善非酒精性脂肪性肝病，并通过巨噬细胞的替代激活促进肝细胞癌的发展。这些肝病与胆汁淤积密切相关。然而，IL-25 是否在胆汁淤积中起重要作用尚不清楚。通过胃内注射α-萘基异硫氰酸酯 (ANIT) 对 IL-25 治疗和 IL-25 敲除 (Il25) 小鼠进行处理，以确定 IL-25 与胆汁淤积之间的生物学关联。在这里，我们发现 IL-25 和 IL-17RB 在 ANIT 诱导的胆汁淤积小鼠中减少。Il25 小鼠表现出 ANIT 诱导的实质损伤加剧，而 IL-25 治疗可显著减轻 ANIT 诱导的胆汁淤积性肝损伤。我们发现 IL-25 降低了肝总胆汁酸的水平，并增加了肝多药耐药相关蛋白 2 (MRP2) 和多药耐药相关蛋白 3 (MRP3) 的表达。总之，IL-25 对 ANIT 诱导的小鼠胆汁淤积性肝损伤具有保护作用，这可能与胆汁酸分泌的调节有关。这些结果为 IL-25 在胆汁淤积性肝病治疗中的应用提供了理论依据。
