Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
EBioMedicine. 2021 Feb;64:103213. doi: 10.1016/j.ebiom.2021.103213. Epub 2021 Jan 25.
Interleukin-24 (IL-24) binds to two kinds of receptor complexes, namely IL-20R1/IL-20R2 and IL-20R2/IL-22R1, which are also bound by IL-20. IL-20 plays a detrimental role in liver fibrosis. Due to the sharing of receptor complexes, we aimed to determine whether IL-24 also participates in liver fibrosis.
Clinical biopsy specimens from various stages of liver fibrosis were used to analyze IL-24 expression. IL-24 protein was administered to mice with thioacetamide (TAA)-induced liver injury. The direct effects of IL-24 on mouse primary hepatocytes or hepatic stellate cells (HSCs) were analyzed. Wild-type, IL-20R1-, and IL20R2-deficient mice were used to establish a model of acute TAA-induced liver injury.
Among patients with more severe liver fibrosis, there was a reduced IL-24/IL-20 ratio. Administration of IL-24 protein protected mice from TAA-induced liver injury and reduction of liver inflammation by antioxidant effects. IL-24 protected hepatocytes from TAA-induced apoptosis and prevented liver fibrosis through the inhibition of the HSCs activation. The protective role of IL-24 acted on liver cells were mainly IL-20R1-independent. IL-20R2-deficient mice exhibited more severe liver injury upon TAA treatment, thus confirming the protective role of IL-24.
IL-24 plays a key protective role in the progression of liver injury and has therapeutic potential for treating liver injuries.
This work was supported by the Ministry of Science and Technology of Taiwan (MOST 106-2320-B-006-024) and Taiwan Liver Disease Prevention & Treatment Research Foundation.
白细胞介素-24（IL-24）结合两种受体复合物，即 IL-20R1/IL-20R2 和 IL-20R2/IL-22R1，IL-20 也能与这两种受体复合物结合。IL-20 在肝纤维化中起有害作用。由于受体复合物的共享，我们旨在确定 IL-24 是否也参与肝纤维化。
使用来自不同阶段肝纤维化的临床活检标本分析 IL-24 表达。给予硫代乙酰胺（TAA）诱导的肝损伤小鼠 IL-24 蛋白。分析 IL-24 对小鼠原代肝细胞或肝星状细胞（HSCs）的直接作用。使用野生型、IL-20R1-和 IL20R2 缺陷型小鼠建立急性 TAA 诱导的肝损伤模型。
在纤维化程度较高的患者中，IL-24/IL-20 比值降低。IL-24 蛋白的给药通过抗氧化作用保护 TAA 诱导的肝损伤小鼠并减少肝炎症。IL-24 通过抑制 HSCs 激活来保护肝细胞免受 TAA 诱导的凋亡并预防肝纤维化。IL-24 对肝细胞的保护作用主要不依赖于 IL-20R1。TAA 处理时，IL-20R2 缺陷型小鼠的肝损伤更严重，从而证实了 IL-24 的保护作用。
IL-24 在肝损伤进展中起关键保护作用，具有治疗肝损伤的治疗潜力。
本工作得到台湾科技部（MOST 106-2320-B-006-024）和台湾肝病防治与研究基金会的支持。
