Key Laboratory of Anti-inflammatory and Immune Medicines, Ministry of Education, School of Pharmacy, Anhui Medical University, 230032 Hefei, China; The Key Laboratory of Major Autoimmune Diseases, Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, 230032 Hefei, China; Institute for Liver Diseases of Anhui Medical University, 230032 Hefei, China.
Key Laboratory of Anti-inflammatory and Immune Medicines, Ministry of Education, School of Pharmacy, Anhui Medical University, 230032 Hefei, China.
Cytokine. 2021 Feb;138:155402. doi: 10.1016/j.cyto.2020.155402. Epub 2020 Dec 22.
Alcoholic fatty liver disease (AFLD) is a disease that causes liver damage due to chronic heavy drinking. AFLD is related to lipid accumulation in liver cells caused by alcohol intake. Interleukin-8 (IL-8) is an inflammatory cytokine associated with chemotaxis (deletion in mice) that has robust effects on the occurrence and development of disease by activating related signal transduction pathways to promote inflammation and cell proliferation. There is significantly increased IL-8 expression in liver disease, which may be related to the pathogenesis of AFLD. In this study, we used hydrodynamic injection to deliver the liver-specific expression vector pLIVE-hIL-8 into mice. We found that hIL-8 can exacerbate alcohol-induced fatty liver disease via the Akt/HIF-1α pathway. Exacerbated liver lipid degeneration in mice, which is characterized by excessive accumulation of triglycerides, and liver damage markers were significantly increased. Moreover, hIL-8 could increase the alcohol-induced release of ROS in fatty liver caused by alcohol and exacerbate fatty liver disease. The expression of liver lipid metabolism-related gene sterol regulatory element-binding protein-1c (SREBP-1c) was increased. Furthermore, the expression of peroxisome proliferator-activated receptor alpha (PPARα), which is related to liver fatty acid oxidation, was decreased. The findings obtained in this study of hIL-8 will help identify a potential target for the clinical treatment of AFLD.
酒精性脂肪肝病（AFLD）是一种由于长期大量饮酒导致肝脏损伤的疾病。AFLD 与酒精摄入引起的肝细胞内脂质堆积有关。白细胞介素-8（IL-8）是一种与趋化作用相关的炎症细胞因子（在小鼠中缺失），通过激活相关信号转导通路促进炎症和细胞增殖，对疾病的发生和发展有很强的影响。在肝病中，IL-8 的表达显著增加，这可能与 AFLD 的发病机制有关。在这项研究中，我们使用流体动力学注射将肝脏特异性表达载体 pLIVE-hIL-8 递送到小鼠体内。我们发现 hIL-8 可以通过 Akt/HIF-1α 通路加剧酒精引起的脂肪肝疾病。酒精引起的肝脂质变性加剧，表现为甘油三酯过度积累，肝损伤标志物显著增加。此外，hIL-8 可增加酒精引起的 ROS 释放，并加剧酒精性脂肪肝疾病。肝脏脂质代谢相关基因固醇调节元件结合蛋白-1c（SREBP-1c）的表达增加。与肝脏脂肪酸氧化相关的过氧化物酶体增殖物激活受体α（PPARα）的表达减少。本研究中对 hIL-8 的研究结果将有助于确定 AFLD 临床治疗的潜在靶点。
