Prostaglandin E2 plays a key role in the immunosuppressive properties of adipose and bone marrow tissue-derived mesenchymal stromal cells

Exp Cell Res. 2010 Nov 15;316(19):3109-23. doi: 10.1016/j.yexcr.2010.08.008. Epub 2010 Sep 8.


Mesenchymal stromal cells (MSCs) have important immunosuppressive properties, but the mechanisms and soluble factors involved in these effects remain unclear. We have studied prostaglandin-E2 (PGE2) as a possible candidate implied in adipose tissue-derived MSCs (Ad-MSCs) immunosuppressive properties over dendritic cells and T lymphocytes, compared to bone marrow derived MSCs (BM-MSCs). We found that both MSCs inhibited the maturation of myeloid-DCs and plasmocytoid-DCs. High levels of PGE2 were detected in DCs/MSCs co-cultures. Its blockade with indomethacin (IDM) allowed plasmocytoid-DCs but not myeloid-DCs maturation. Additionally, high levels of PGE2 were found in co-cultures in which Ad-MSCs or BM-MSCs inhibited activated T cells proliferation and pro-inflammatory cytokines production. PGE2 blockade by IDM preserved T lymphocytes proliferation but did not restore the pro-inflammatory cytokines secretion. However, an increased expression of transcription factors and cytokines genes involved in the Th1/Th2 differentiation pathway was detected in the T cells co-cultured with Ad-MSCs, but not with BM-MSCs. In conclusion, we propose that PGE2 is a soluble factor mediating most of the immunosuppressive effects of Ad-MSCs and BM-MSCs over p-DCs maturation and activated T lymphocytes proliferation and cytokine secretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Bone Marrow Cells / cytology*
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Coculture Techniques
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dinoprostone / metabolism*
  • Gene Expression Regulation / drug effects
  • Humans
  • Immune Tolerance / drug effects
  • Immune Tolerance / immunology*
  • Immunophenotyping
  • Indomethacin / pharmacology
  • Lymphocyte Activation / drug effects
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / immunology*
  • Mitogens / pharmacology
  • Phytohemagglutinins / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Stromal Cells / cytology
  • Stromal Cells / drug effects
  • Stromal Cells / immunology*
  • Th1 Cells / cytology
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th2 Cells / cytology
  • Th2 Cells / drug effects
  • Th2 Cells / immunology


  • Cytokines
  • Mitogens
  • Phytohemagglutinins
  • RNA, Messenger
  • Dinoprostone
  • Indomethacin