Activation of NOD-1/JNK/IL-8 signal axis in decidual stromal cells facilitates trophoblast invasion

Am J Reprod Immunol. 2017 Aug;78(2). doi: 10.1111/aji.12672. Epub 2017 Mar 22.

Abstract

Decidual stromal cells (DSCs) are known to regulate trophoblast invasion via unveiled mechanism yet. And nucleotide-binding oligomerization domain-containing protein 1 (NOD1) may influence on this DSC-trophoblast interaction. We investigated the mechanism underlying the DSC-mediated regulation of trophoblast invasion and the effect of NOD1 on their cross talk. Using human primary DSCs, BeWo cell invasion was measured. Cytokine secretion and MAP kinase signaling were examined in DSCs following treatment with NOD1 agonist, Tri-DAP. DSCs secreted IL-8 and increased trophoblast invasion. Tri-DAP further increased IL-8 secretion from DSCs via JNK pathway and facilitated both MMP-2 production and trophoblast invasion compared with control. Upon cotreatment of IL-8 and anti-IL-8 antibody to BeWo cells, the number of invading trophoblasts and MMP-2 production decreased significantly. These results suggest that IL-8 from DSCs may play a role to increase the invasiveness of trophoblast cells into the decidua via NOD1/JNK pathway.

Keywords: c-Jun N-terminal kinase; decidual stromal cell; interleukin-8; nucleotide-binding oligomerization domain-containing protein 1; pre-eclampsia trophoblast.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Cells, Cultured
  • Decidua / cytology
  • Decidua / metabolism*
  • Female
  • Humans
  • Interleukin-8 / metabolism*
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Nod1 Signaling Adaptor Protein / metabolism
  • Pregnancy
  • Pregnancy Trimester, First
  • Signal Transduction
  • Stromal Cells / metabolism
  • Trophoblasts / physiology*

Substances

  • CXCL8 protein, human
  • Interleukin-8
  • NOD1 protein, human
  • Nod1 Signaling Adaptor Protein
  • JNK Mitogen-Activated Protein Kinases