A protective role of IL-30 via STAT and ERK signaling pathways in macrophage-mediated inflammation

Biochem Biophys Res Commun. 2013 May 31;435(2):306-12. doi: 10.1016/j.bbrc.2013.03.136. Epub 2013 Apr 11.


IL-30, the p28 subunit of IL-27, interacts with the Epstein-Barr virus-induced gene 3 (EBI3) to form IL-27, which modulates the inflammatory responses in autoimmune and infectious diseases. Several previous studies have provided evidence for the role of IL-30 in the anti-inflammatory process. However, the effect of IL-30 in macrophage-mediated immune responses is not well understood. With the recent observation in our experiment, we found that IL-30 exerted potent anti-inflammatory effects in the RAW 264.7 macrophages and in a lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced mouse model. IL-30 decreased the production of tumor necrosis factor (TNF)-α and IL-6 in LPS-stimulated RAW 264.7 macrophages in a dose-dependent manner. In the macrophage-mediated GalN and LPS model of acute liver injury, IL-30 prevented liver injury by suppressing serum enzyme activity and down-regulating the pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and interferon (IFN)-γ. IL-30 treatment decreased apoptosis in liver tissue and increased glutathione (GSH) levels. We postulated that IL-30 might function through gp130-mediated signaling pathways and then demonstrated that IL-30 affects LPS-induced inflammation through the STAT1, STAT3, and ERK signaling pathways. These data indicate that IL-30 can provide critical protection against macrophage-mediated liver inflammation through anti-apoptotic, anti-oxidant, and anti-inflammatory activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Hepatitis / immunology*
  • Hepatitis / pathology*
  • Immunologic Factors / immunology
  • Interleukin-6 / immunology*
  • Interleukins / immunology*
  • MAP Kinase Signaling System / immunology*
  • Macrophage Activation / immunology*
  • Macrophages / immunology*
  • Mice
  • Mice, Inbred ICR
  • STAT Transcription Factors


  • Il27 protein, mouse
  • Immunologic Factors
  • Interleukin-6
  • Interleukins
  • STAT Transcription Factors