IFN-τ Plays an Anti-Inflammatory Role in Staphylococcus aureus-Induced Endometritis in Mice Through the Suppression of NF-κB Pathway and MMP9 Expression

J Interferon Cytokine Res. 2017 Feb;37(2):81-89. doi: 10.1089/jir.2016.0058. Epub 2016 Nov 15.

Abstract

Interferon-tau (IFN-τ) is a type I interferon and considered as a pregnancy recognition signal in ruminants. Our previous reports have confirmed that IFN-τ has a potential anti-inflammatory effect in macrophage. However, the anti-inflammatory effect of IFN-τ on endometritis has never been reported. Thus, the aim of this study was to investigate the effects of IFN-τ in a mouse model of Staphylococcus aureus-induced endometritis. The histopathological and myeloperoxidase activity results showed that IFN-τ could protect the uterus from S. aureus damage. Enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction results revealed that IFN-τ inhibited TNF-α, IL-1β, and IL-6 production. TLR2, involved in the S. aureus infection, was downregulated by IFN-τ and directly activated nuclear transcription factor kappa-B (NF-κB) pathway. Then, we measured the phosphorylation of IκBα and NF-κB p65 by Western blotting. Western blotting results indicated that IFN-τ inhibited the phosphorylation of IκBα and NF-κB p65 in the S. aureus-induced endometritis. Matrix metalloproteinase (MMP)9, which has been reported to be regulated by NF-κB, was also suppressed by IFN-τ, but its inhibitors, tissue inhibitor of metalloproteinases1 level, increased. All of these findings suggested that IFN-τ plays an anti-inflammatory role in S. aureus-induced endometritis by suppressing NF-κB pathway and MMP9 expression.

Keywords: IFN-τ; MMP9; NF-κB; S. aureus; endometritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Endometritis / drug therapy
  • Endometritis / metabolism*
  • Endometritis / microbiology*
  • Endometritis / pathology
  • Enzyme Activation
  • Female
  • Gene Expression Regulation / drug effects
  • Inflammation Mediators / metabolism
  • Interferon Type I / pharmacology*
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • Mice
  • NF-kappa B / metabolism*
  • Peroxidase / metabolism
  • Signal Transduction / drug effects*
  • Staphylococcus aureus / drug effects*
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / metabolism

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Inflammation Mediators
  • Interferon Type I
  • NF-kappa B
  • Toll-Like Receptor 2
  • Peroxidase
  • Matrix Metalloproteinase 9