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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding Sites
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Case-Control Studies
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Cell Line
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Cyclic AMP Response Element-Binding Protein / metabolism
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Cyclic AMP-Dependent Protein Kinases / physiology*
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Cyclooxygenase 2 / metabolism*
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Dinoprostone / blood
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Dogs
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Enzyme Activation
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Humans
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Influenza A Virus, H1N1 Subtype / physiology*
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Influenza A Virus, H3N2 Subtype / physiology*
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Influenza, Human / blood
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Influenza, Human / enzymology*
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Influenza, Human / virology
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Interleukins / blood
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Interleukins / genetics
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Interleukins / metabolism*
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Leukocytes, Mononuclear / metabolism
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Leukocytes, Mononuclear / virology
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Minor Histocompatibility Antigens
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Phosphorylation
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Promoter Regions, Genetic
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STAT Transcription Factors / metabolism
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Signal Transduction
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Transcriptional Activation
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Virus Replication
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eIF-2 Kinase / metabolism
Substances
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CREB1 protein, human
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Cyclic AMP Response Element-Binding Protein
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EBI3 protein, human
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Interleukins
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MYDGF protein, human
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Minor Histocompatibility Antigens
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STAT Transcription Factors
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Cyclooxygenase 2
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PTGS2 protein, human
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eIF-2 Kinase
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Cyclic AMP-Dependent Protein Kinases
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Dinoprostone