Division of Experimental Immunology and Hepatology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
Hepatology. 2010 Feb;51(2):398-404. doi: 10.1002/hep.23339.
The anti-inflammatory and antiapoptotic heme degrading enzyme heme oxygenase-1 (HO-1) has been shown recently to interfere with replication of hepatitis C virus (HCV). We investigated the effect of HO-1 products carbon monoxide (CO), iron and biliverdin on HCV replication using the replicon cell lines Huh-5-15 and LucUbiNeo-ET, stably expressing HCV proteins NS3 through NS5B. Incubation of these cell lines in the presence of the CO donor methylene chloride transiently reduced HCV replication, whereas an increase of iron in cell culture by administration of FeCl(3) or iron-saturated lactoferrin did not interfere with HCV replication. Likewise, depletion of iron by deferoxamine during induction of HO-1 by cobalt-protoporphyrin IX did not restore HCV replication. The most prominent effect was observed after incubation of replicon cell lines in the presence of biliverdin. Biliverdin seems to interfere with HCV replication-mediated oxidative stress by inducing expression of antiviral interferons, such as interferon alpha2 and alpha17.
The antioxidant biliverdin reduces HCV replication in vitro by triggering the antiviral interferon response and might improve HCV therapy in the future.
最近研究表明，具有抗炎和抗细胞凋亡作用的血红素降解酶血红素加氧酶-1（HO-1）可干扰丙型肝炎病毒（HCV）的复制。我们使用稳定表达 HCV 蛋白 NS3 至 NS5B 的 Huh-5-15 和 LucUbiNeo-ET 复制子细胞系研究了 HO-1 产物一氧化碳（CO）、铁和胆红素对 HCV 复制的影响。这些细胞系在 CO 供体二氯甲烷存在下孵育时，HCV 复制会短暂减少，而通过施用 FeCl3 或铁饱和乳铁蛋白增加细胞培养中的铁则不会干扰 HCV 复制。同样，在用钴原卟啉 IX 诱导 HO-1 时用去铁胺耗竭铁也不会恢复 HCV 复制。在存在胆红素的情况下孵育复制子细胞系后观察到最显著的效果。胆红素通过诱导抗病毒干扰素（如干扰素-α2 和-α17）的表达似乎干扰了 HCV 复制介导的氧化应激。
抗氧化剂胆红素通过触发抗病毒干扰素反应减少体外 HCV 复制，将来可能会改善 HCV 治疗。
