Department of Clinical Laboratory, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China (mainland).
Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China (mainland).
Med Sci Monit. 2018 Jul 4;24:4617-4624. doi: 10.12659/MSM.906250.
BACKGROUND Reactivation of hepatitis B virus (HBV) is a fatal complication of chemotherapy. Occult HBV infection might be reactivated in patients undergoing chemotherapy or immunosuppression. However, the mechanism of HBV reactivation induced by chemotherapy or immunosuppression remains unclear. MATERIAL AND METHODS HepG2.2.15 cells were treated with an autophagy inducer (rapamycin), an inhibitor (3-methyladenine, 3-MA), and dexamethasone. Autophagosomes were observed by a transmission electron microscope (TEM). LC3-I, LC3-II, and P62 were analyzed by western blot. HBV replicative intermediates were detected by southern blot. HBV DNA expression was quantitated with real-time polymerase chain reaction (PCR). The level of HBV surface antigen (HBsAg) in culture medium was examined by ELISA. RESULTS In this study, we find that dexamethasone stimulates HBV replication and protein expression by inducing autophagy in HepG2.2.15 cells. In contrast, autophagy inhibitor (3-MA) abrogates HBsAg secretion stimulated by dexamethasone. CONCLUSIONS Our results suggest that dexamethasone stimulates HBV replication through autophagy. This might provide a novel insight into the mechanism of glucocorticoid-mediated HBV reactivation through autophagy, which might be a new therapeutic target.
乙型肝炎病毒（HBV）的再激活是化疗的致命并发症。隐匿性 HBV 感染可能在接受化疗或免疫抑制的患者中被再激活。然而，化疗或免疫抑制诱导 HBV 再激活的机制仍不清楚。
用自噬诱导剂（雷帕霉素）、抑制剂（3-甲基腺嘌呤，3-MA）和地塞米松处理 HepG2.2.15 细胞。用透射电子显微镜（TEM）观察自噬体。用 Western blot 分析 LC3-I、LC3-II 和 P62。用 Southern blot 检测 HBV 复制中间体。用实时聚合酶链反应（PCR）定量 HBV DNA 表达。用 ELISA 检测培养上清液中的 HBV 表面抗原（HBsAg）水平。
在这项研究中，我们发现地塞米松通过诱导 HepG2.2.15 细胞中的自噬来刺激 HBV 复制和蛋白表达。相比之下，自噬抑制剂（3-MA）可阻断地塞米松刺激的 HBsAg 分泌。
我们的结果表明，地塞米松通过自噬刺激 HBV 复制。这可能为糖皮质激素通过自噬介导 HBV 再激活的机制提供新的见解，这可能是一个新的治疗靶点。
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