Chronic hepatitis C virus (HCV) infection accounts for a large proportion of hepatic fibrosis and carcinoma cases observed worldwide. Mechanisms involved in HCV-induced hepatic injury have yet to be fully elucidated. Of particular interest is the capacity of HCV to regulate inflammatory responses. Here, we reveal modulation of cytokine activity by the HCV proteins non-structural protein 3 (NS3), glycoprotein E2, and core protein for their ability to induce chemokine expression in various liver bystander cells. Chemokines sustain chronic liver inflammation and relay multiple fibrogenic effects. CCL2, CCL3, CCL20, CXCL8, and CXCL10 were differentially expressed after treatment of monocytes, fibroblasts, or liver sinusoidal microvascular endothelial cells (LSECs) with HCV proteins. In comparison to NS3 and glycoprotein E2, core protein was a stronger inducer of chemokines in liver bystander cells. Interferon-γ (IFN-γ) and interleukin-1β (IL-1β) synergized with core protein to induce CCL2, CCL20, CXCL8, or CXCL10 in fibroblasts or LSECs. These findings reveal new mechanisms of hepatic injury caused by HCV.

中文翻译：

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丙型肝炎病毒蛋白对趋化因子的诱导：核心蛋白与肝旁观细胞中的白细胞介素-1β 和干扰素-γ 的协同作用。

慢性丙型肝炎病毒 (HCV) 感染占全球观察到的肝纤维化和癌症病例的很大比例。HCV 引起的肝损伤的机制尚未完全阐明。特别令人感兴趣的是 HCV 调节炎症反应的能力。在这里，我们揭示了 HCV 蛋白非结构蛋白 3 (NS3)、糖蛋白 E2 和核心蛋白对细胞因子活性的调节，因为它们具有在各种肝脏旁观细胞中诱导趋化因子表达的能力。趋化因子维持慢性肝脏炎症并传递多种纤维化作用。CCL2、CCL3、CCL20、CXCL8 和 CXCL10 在用 HCV 蛋白处理单核细胞、成纤维细胞或肝窦微血管内皮细胞 (LSEC) 后差异表达。与 NS3 和糖蛋白 E2 相比，核心蛋白是肝旁观细胞中更强的趋化因子诱导剂。干扰素-γ (IFN-γ) 和白介素-1β (IL-1β) 与核心蛋白协同诱导成纤维细胞或 LSEC 中的 CCL2、CCL20、CXCL8 或 CXCL10。这些发现揭示了HCV引起的肝损伤的新机制。