Department of Pharmacy, Xiamen Medical College, Xiamen 361023, China.
Department of Biotechnology, Quanzhou Normal University, Quanzhou 362000, China.
J Agric Food Chem. 2022 Feb 23;70(7):2211-2220. doi: 10.1021/acs.jafc.1c06681. Epub 2022 Feb 8.
Iron deposition and chronic inflammation are associated with chronic liver diseases, such as alcoholic liver disease, nonalcoholic fatty liver disease, and chronic hepatitis B and C. However, the relationship between iron deposition and chronic inflammation in these diseases is still unclear. In the current study, we aimed to investigate the effect of iron on chronic inflammation in HepG2 cells and mice liver. We demonstrated that iron treatment enhanced the expression of cGAS, STING, and their downstream targets, including TBK1, IRF-3, and NF-κB in HepG2 cells and mice liver. We also found that treatment of HepG2 cells and mice with ferric ammonium citrate increased the expression of inflammatory cytokines, such as IFN-β. Finally, we found that genes involved in iron metabolism and the STING signaling pathway were up-regulated in liver cancer tissues, and the survival time of patients with high expression of these genes in tumor tissues was significantly shortened. These results suggest that iron overload may promote the progress of the chronic liver disease by activating cGAS-STING-mediated chronic inflammation, which provides a new idea for the development of drugs for the treatment of the chronic liver disease.
铁沉积和慢性炎症与慢性肝病有关，如酒精性肝病、非酒精性脂肪性肝病和慢性乙型肝炎和丙型肝炎。然而，这些疾病中铁沉积与慢性炎症之间的关系尚不清楚。在本研究中，我们旨在研究铁对 HepG2 细胞和小鼠肝脏慢性炎症的影响。结果表明，铁处理增强了 HepG2 细胞和小鼠肝脏中 cGAS、STING 及其下游靶标（包括 TBK1、IRF-3 和 NF-κB）的表达。我们还发现，用柠檬酸铁铵处理 HepG2 细胞和小鼠会增加 IFN-β等炎症细胞因子的表达。最后，我们发现铁代谢基因和 STING 信号通路相关基因在肝癌组织中上调，肿瘤组织中这些基因高表达的患者的生存时间明显缩短。这些结果表明，铁过载可能通过激活 cGAS-STING 介导的慢性炎症促进慢性肝病的进展，这为治疗慢性肝病的药物开发提供了新的思路。
