Avian leukosis virus subgroup J induces VEGF expression via NF-κB/PI3K-dependent IL-6 production.
Avian leukosis virus subgroup J induces VEGF expression via NF-κB/PI3K-dependent IL-6 production.
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禽白血病病毒 J 亚型通过 NF-κB/PI3K 依赖性 IL-6 产生诱导 VEGF 表达
DOI：
10.18632/oncotarget.13282
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发表时间：
2016-12-06
期刊：
影响因子：
--
通讯作者：
Gao Y
中科院分区：
文献类型：
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作者：
Gao Y;Zhang Y;Yao Y;Guan X;Liu Y;Qi X;Wang Y;Liu C;Zhang Y;Gao H;Nair V;Wang X;Gao Y
J亚群禽白血病病毒(ALV-J)是一种能引起鸡血管瘤和骨髓瘤的致癌病毒。白介素6(IL-6)是一种多功能的促炎性白介素2，参与多种癌症的发生。我们先前在鸡ALV-J感染后证明了IL-6的表达被诱导。本研究旨在探讨ALV-J诱导IL-6表达的机制，以及IL-6在肿瘤发生发展中的作用。我们的结果表明，ALV-J感染增加了鸡脾细胞、外周血淋巴细胞和血管内皮细胞IL-6的表达。IL-6的产生是由ALV-J囊膜蛋白gp85和衣壳蛋白p27通过PI3K和NF-κB介导的信号途径诱导的。IL-6可诱导血管内皮细胞和胚胎血管组织表达血管内皮生长因子-A及其受体VEGFR-2。用siRNA抑制IL-6可抑制ALV-J诱导的血管内皮细胞VEGF-A和VEGFR-2的表达，提示ALV-J诱导的VEGF-A/VEGFR-2的表达是由IL-6介导的。由于VEGF-A和VEGFR-2是肿瘤发生中的重要因子，我们的研究结果提示ALV-J劫持IL-6以促进肿瘤的发生，并提示IL-6可能成为ALV-J感染的治疗靶点。
Avian leukosis virus subgroup J (ALV-J) is an oncogenic virus causing hemangiomas and myeloid tumors in chickens. Interleukin-6 (IL-6) is a multifunctional pro-inflammatory interleukin involved in many types of cancer. We previously demonstrated that IL-6 expression was induced following ALV-J infection in chickens. The aim of this study is to characterize the mechanism by which ALV-J induces IL-6 expression, and the role of IL-6 in tumor development. Our results demonstrate that ALV-J infection increases IL-6 expression in chicken splenocytes, peripheral blood lymphocytes, and vascular endothelial cells. IL-6 production is induced by the ALV-J envelope protein gp85 and capsid protein p27 via PI3K- and NF-κB-mediated signaling. IL-6 in turn induced expression of vascular endothelial growth factor (VEGF)-A and its receptor, VEGFR-2, in vascular endothelial cells and embryonic vascular tissues. Suppression of IL-6 using siRNA inhibited the ALV-J induced VEGF-A and VEGFR-2 expression in vascular endothelial cells, indicating that the ALV-J-induced VEGF-A/VEGFR-2 expression is mediated by IL-6. As VEGF-A and VEGFR-2 are important factors in oncogenesis, our findings suggest that ALV-J hijacks IL-6 to promote tumorigenesis, and indicate that IL-6 could potentially serve as a therapeutic target in ALV-J infections.