Interleukin-27 Enhances the Potential of Reactive Oxygen Species Generation From Monocyte-derived Macrophages and Dendritic Cells by Induction of p47 phox

Sci Rep. 2017 Feb 27;7:43441. doi: 10.1038/srep43441.

Abstract

Interleukin (IL)-27, a member of the IL-12 cytokine family, plays an important and diverse role in the function of the immune system. We have previously demonstrated that IL-27 is an anti-viral cytokine which inhibits HIV-1, HIV-2, Influenza virus and herpes simplex virus infection, and enhances the potential of reactive oxygen species (ROS) generating activity during differentiation of monocytes to macrophages. In this study, we further investigated the mechanism of the enhanced potential for ROS generation by IL-27. Real time PCR, western blot and knock down assays demonstrate that IL-27 is able to enhance the potential of superoxide production not only during differentiation but also in terminally differentiated-macrophages and immature dendritic cells (iDC) in association with the induction of p47phox, a cytosolic component of the ROS producing enzyme, NADPH oxidase, and the increase in amounts of phosphorylated p47phox upon stimulation. We also demonstrate that IL-27 is able to induce extracellular superoxide dismutase during differentiation of monocytes but not in terminal differentiated macrophages. Since ROS plays an important role in a variety of inflammation, our data demonstrate that IL-27 is a potent regulator of ROS induction and may be a novel therapeutic target.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Differentiation / drug effects
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Gene Expression Regulation
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Humans
  • Interleukin-4 / pharmacology
  • Interleukins / pharmacology*
  • Macrophage Activation / drug effects
  • Macrophage Colony-Stimulating Factor / pharmacology
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Macrophages / immunology
  • NADPH Oxidases / genetics*
  • NADPH Oxidases / immunology
  • Phosphorylation / drug effects
  • Primary Cell Culture
  • Signal Transduction
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / immunology
  • Superoxides / immunology
  • Superoxides / metabolism*

Substances

  • IL27 protein, human
  • IL4 protein, human
  • Interleukins
  • Superoxides
  • Interleukin-4
  • Macrophage Colony-Stimulating Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Superoxide Dismutase
  • NADPH Oxidases
  • neutrophil cytosolic factor 1