Transcriptomics and Immunological Analyses Reveal a Pro-Angiogenic and Anti-Inflammatory Phenotype for Decidual Endothelial Cells

Int J Mol Sci. 2019 Mar 31;20(7):1604. doi: 10.3390/ijms20071604.

Abstract

Background: In pregnancy, excessive inflammation and break down of immunologic tolerance can contribute to miscarriage. Endothelial cells (ECs) are able to orchestrate the inflammatory processes by secreting pro-inflammatory mediators and bactericidal factors by modulating leakiness and leukocyte trafficking, via the expression of adhesion molecules and chemokines. The aim of this study was to analyse the differences in the phenotype between microvascular ECs isolated from decidua (DECs) and ECs isolated from human skin (ADMECs).

Methods: DECs and ADMECs were characterized for their basal expression of angiogenic factors and adhesion molecules. A range of immunological responses was evaluated, such as vessel leakage, reactive oxygen species (ROS) production in response to TNF-α stimulation, adhesion molecules expression and leukocyte migration in response to TNF-α and IFN-γ stimulation.

Results: DECs produced higher levels of HGF, VEGF-A and IGFBP3 compared to ADMECs. DECs expressed adhesion molecules, ICAM-2 and ICAM-3, and a mild response to TNF-α was observed. Finally, DECs produced high levels of CXCL9/MIG and CXCL10/IP-10 in response to IFN-γ and selectively recruited Treg lymphocytes.

Conclusion: DEC phenotype differs considerably from that of ADMECs, suggesting that DECs may play an active role in the control of immune response and angiogenesis at the foetal-maternal interface.

Keywords: angiogenesis; decidua; endothelium; inflammation; skin.

MeSH terms

  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cells, Cultured
  • Chemokine CXCL10 / genetics
  • Chemokine CXCL10 / metabolism
  • Chemokine CXCL9 / genetics
  • Chemokine CXCL9 / metabolism
  • Decidua
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • In Vitro Techniques
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / metabolism
  • Intercellular Adhesion Molecule-3 / genetics
  • Intercellular Adhesion Molecule-3 / metabolism
  • Interferon-gamma / pharmacology
  • Neovascularization, Pathologic / genetics*
  • Neovascularization, Pathologic / immunology*
  • Neovascularization, Pathologic / metabolism
  • Pregnancy
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin / drug effects
  • Skin / immunology*
  • Skin / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Antigens, CD
  • CXCL9 protein, human
  • Cell Adhesion Molecules
  • Chemokine CXCL10
  • Chemokine CXCL9
  • ICAM2 protein, human
  • ICAM3 protein, human
  • Intercellular Adhesion Molecule-3
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma