Transcriptomics and Immunological Analyses Reveal a Pro-Angiogenic and Anti-Inflammatory Phenotype for Decidual Endothelial Cells.
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.
['Agostinis|Chiara|C|', 'Masat|Elisa|E|', 'Bossi|Fleur|F|', 'Ricci|Giuseppe|G|', 'Menegazzi|Renzo|R|', 'Lombardelli|Letizia|L|', 'Zito|Gabriella|G|', 'Mangogna|Alessandro|A|0000-0001-7910-1274', 'Degan|Massimo|M|', 'Gattei|Valter|V|', 'Piccinni|Marie-Pierre|MP|0000-0003-1810-5209', 'Kishore|Uday|U|', 'Bulla|Roberta|R|0000-0003-1737-5776']
D015703:Antigens, CD D015815:Cell Adhesion Molecules D002478:Cells, Cultured D054357:Chemokine CXCL10 D054370:Chemokine CXCL9 D003656:Decidua D042783:Endothelial Cells D005260:Female D005455:Fluorescent Antibody Technique D006801:Humans D066298:In Vitro Techniques D007249:Inflammation D000074001:Intercellular Adhesion Molecule-3 D007371:Interferon-gamma D009389:Neovascularization, Pathologic D011247:Pregnancy D020133:Reverse Transcriptase Polymerase Chain Reaction D012867:Skin D014409:Tumor Necrosis Factor-alpha
inflammation decidua skin angiogenesis endothelium