title: Influenza A virus induces interleukin-27 through cyclooxygenase-2 and protein kinase A signaling.
abstract: 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.
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Zhongying
authors.initials: Z
authors.lastname: Cao
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Cao
authors.forename: Chengliang
authors.initials: C
authors.lastname: Zhu
authors.forename: Kailang
authors.initials: K
authors.lastname: Wu
authors.forename: Jianguo
authors.initials: J
authors.lastname: Wu
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001665:Binding Sites; D016022:Case-Control Studies; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000097:blood; D004285:Dogs; D004789:Enzyme Activation; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D053122:Influenza A Virus, H3N2 Subtype / Q000502:physiology*; D007251:Influenza, Human / Q000097:blood / Q000201:enzymology* / Q000821:virology; D007378:Interleukins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology; D015778:Minor Histocompatibility Antigens; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation; D014779:Virus Replication; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; C097732:EBI3 protein, human; D007378:Interleukins; C464565:MYDGF protein, human; D015778:Minor Histocompatibility Antigens; D050791:STAT Transcription Factors; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019892:eIF-2 Kinase; D017868:Cyclic AMP-Dependent Protein Kinases; D015232:Dinoprostone