IFN-τ Alleviates Lipopolysaccharide-Induced Inflammation by Suppressing NF-κB and MAPKs Pathway Activation in Mice

Inflammation. 2016 Jun;39(3):1141-50. doi: 10.1007/s10753-016-0348-9.

Abstract

IFN-τ, which is a type I interferon with low cytotoxicity, is defined as a pregnancy recognition signal in ruminants. Type I interferons have been used as anti-inflammatory agents, but their side effects limit their clinical application. The present study aimed to determine the anti-inflammatory effects of IFN-τ in a lipopolysaccharide-stimulated acute lung injury (ALI) model and in RAW264.7 cells and to confirm the mechanism of action involved. The methods used included histopathology, measuring the lung wet/dry ratio, determining the myeloperoxidase activity, ELISA, qPCR, and western blot. The results revealed that IFN-τ greatly ameliorated the infiltration of inflammatory cells and the expression of TNF-α, IL-1β, and IL-6. Further analysis revealed that IFN-τ down-regulated the expression of TLR-2 and TLR-4 mRNA and the activity of the NF-κB and MAPK pathways both in a lipopolysaccharide-induced ALI model and in RAW264.7 cells. The results demonstrated that IFN-τ suppressed the levels of pro-inflammatory cytokines by inhibiting the phosphorylation of the NF-κB and MAPK pathways. Thus, IFN-τ may be an optimal target for the treatment of inflammatory diseases.

Keywords: IFN-τ; LPS; MAPKs; NF-κB; anti-inflammation.

MeSH terms

  • Acute Lung Injury / drug therapy
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Cytokines / drug effects
  • Disease Models, Animal
  • Female
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Interferon Type I / pharmacology*
  • Lipopolysaccharides
  • MAP Kinase Signaling System / drug effects*
  • Mice
  • NF-kappa B / antagonists & inhibitors*
  • Phosphorylation
  • Pregnancy Proteins / pharmacology*
  • RAW 264.7 Cells
  • Signal Transduction

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Interferon Type I
  • Lipopolysaccharides
  • NF-kappa B
  • Pregnancy Proteins
  • interferon tau