Influenza A Virus Induces Interleukin-27 through Cyclooxygenase-2 and Protein Kinase A Signaling

作者：Li Liu, Zhongying Cao, Jing Chen, Rui Li, Yanhua Cao, Chengliang Zhu, Chengliang Zhu, Kailang Wu, Jianguo Wu, Fang Liu, Ying Zhu · 发表于：Journal of Biological Chemistry · 年份：2012 · DOI：10.1074/jbc.m111.308064 · 被引用次数：73 · 研究领域：Cytokine Signaling Pathways and Interactions、Immune Response and Inflammation、Adrenal Hormones and Disorders

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.