State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
J Biol Chem. 2012 Apr 6;287(15):11899-910. doi: 10.1074/jbc.M111.308064. Epub 2012 Feb 16.
We previously reported that IL-27, which belongs to the IL-12 family of cytokines, is elevated in the serum of patients infected with influenza A virus (IAV). Here, we show that the expression of IL-27 was significantly up-regulated in A549 human lung epithelial cells and human peripheral blood mononuclear cells infected with IAV. Additionally, IAV triggered IL-27 expression through protein kinase A and cAMP-response element-binding protein signaling, which was mediated by cyclooxygenase-2-derived prostaglandin E(2). IL-27 inhibited IAV replication by STAT1/2/3 phosphorylation and activated antiviral factor protein kinase R phosphorylation. Clinical analysis showed that IL-27 levels were significantly elevated in a cohort of patients infected with IAV compared with healthy individuals and that circulating IL-27 levels were tightly and positively correlated with prostaglandin E(2) levels. These results indicate that IL-27 expression is one host immune factor produced in response to IAV infection and that elevated IL-27 levels inhibit viral replication.
我们之前曾报道过，属于白细胞介素-12 家族细胞因子的白细胞介素-27（IL-27）在感染甲型流感病毒（IAV）的患者血清中升高。在这里，我们发现 A549 人肺上皮细胞和人外周血单个核细胞感染 IAV 后，IL-27 的表达显著上调。此外，IAV 通过蛋白激酶 A 和 cAMP 反应元件结合蛋白信号触发 IL-27 的表达，这是由环氧化酶-2 衍生的前列腺素 E2（PGE2）介导的。IL-27 通过 STAT1/2/3 磷酸化抑制 IAV 复制，并激活抗病毒因子蛋白激酶 R 磷酸化。临床分析显示，与健康个体相比，IAV 感染患者的 IL-27 水平显著升高，循环 IL-27 水平与前列腺素 E2（PGE2）水平呈紧密正相关。这些结果表明，IL-27 的表达是宿主对 IAV 感染产生的一种免疫因子，升高的 IL-27 水平抑制病毒复制。
