Influenza A virus induces interleukin-27 through cyclooxygenase-2 and protein kinase A signaling

J Biol Chem. 2012 Apr 6;287(15):11899-910. doi: 10.1074/jbc.M111.308064. Epub 2012 Feb 16.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Case-Control Studies
  • Cell Line
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Cyclic AMP-Dependent Protein Kinases / physiology*
  • Cyclooxygenase 2 / metabolism*
  • Dinoprostone / blood
  • Dogs
  • Enzyme Activation
  • Humans
  • Influenza A Virus, H1N1 Subtype / physiology*
  • Influenza A Virus, H3N2 Subtype / physiology*
  • Influenza, Human / blood
  • Influenza, Human / enzymology*
  • Influenza, Human / virology
  • Interleukins / blood
  • Interleukins / genetics
  • Interleukins / metabolism*
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / virology
  • Minor Histocompatibility Antigens
  • Phosphorylation
  • Promoter Regions, Genetic
  • STAT Transcription Factors / metabolism
  • Signal Transduction
  • Transcriptional Activation
  • Virus Replication
  • eIF-2 Kinase / metabolism

Substances

  • CREB1 protein, human
  • Cyclic AMP Response Element-Binding Protein
  • EBI3 protein, human
  • Interleukins
  • MYDGF protein, human
  • Minor Histocompatibility Antigens
  • STAT Transcription Factors
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • eIF-2 Kinase
  • Cyclic AMP-Dependent Protein Kinases
  • Dinoprostone