PMID- 20207200 OWN - NLM STAT- MEDLINE DCOM- 20100609 LR - 20181201 IS - 1521-7035 (Electronic) IS - 1521-6616 (Linking) VI - 135 IP - 3 DP - 2010 Jun TI - Human umbilical cord mesenchymal stem cells hUC-MSCs exert immunosuppressive activities through a PGE2-dependent mechanism. PG - 448-58 LID - 10.1016/j.clim.2010.01.015 [doi] AB - Human umbilical-cord-derived mesenchymal stem cells (hUC-MSCs) constitute an attractive alternative to bone-marrow-derived MSCs for potential clinical applications because of easy preparation and lower risk of viral contamination. In this study, both proliferation of human peripheral blood mononuclear cells (hPBMCs) and their IFN-gamma production in response to mitogenic or allogeneic stimulus were effectively inhibited by hUC-MSCs. Co-culture experiments in transwell systems indicated that the suppression was largely mediated by soluble factor(s). Blocking experiments identified prostaglandin E(2) (PGE(2)) as the major factor, because inhibition of PGE(2) synthesis almost completely mitigated the immunosuppressive effects, whereas neutralization of TGF-beta, IDO, and NO activities had little effects. Moreover, the inflammatory cytokines, IFN-gamma and IL-1beta, produced by hPBMCs upon activation notably upregulated the expression of cyclooxygenase-2 (COX-2) and the production of PGE(2) by hUC-MSCs. In conclusion, our data have demonstrated for the first time the PGE(2)-mediated mechanism by which hUC-MSCs exert their immunomodulatory effects. CI - Copyright 2010 Elsevier Inc. All rights reserved. FAU - Chen, Ke AU - Chen K AD - The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, Tianjin 300020, China. FAU - Wang, Ding AU - Wang D FAU - Du, Wei Ting AU - Du WT FAU - Han, Zhi-Bo AU - Han ZB FAU - Ren, He AU - Ren H FAU - Chi, Ying AU - Chi Y FAU - Yang, Shao Guang AU - Yang SG FAU - Zhu, Delin AU - Zhu D FAU - Bayard, Francis AU - Bayard F FAU - Han, Zhong Chao AU - Han ZC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100305 PL - United States TA - Clin Immunol JT - Clinical immunology (Orlando, Fla.) JID - 100883537 RN - 0 (Cytokines) RN - 0 (RNA, Messenger) RN - 82115-62-6 (Interferon-gamma) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - Cell Proliferation MH - Cell Separation MH - Coculture Techniques MH - Cyclooxygenase 2/immunology/metabolism MH - Cytokines/biosynthesis/immunology MH - Dinoprostone/*immunology/metabolism MH - Enzyme-Linked Immunosorbent Assay MH - Fetal Blood/cytology/immunology/metabolism MH - Flow Cytometry MH - Gene Expression/immunology MH - Humans MH - Immune Tolerance/*immunology MH - Immunophenotyping MH - Interferon-gamma/biosynthesis/immunology MH - Leukocytes, Mononuclear/*immunology MH - Mesenchymal Stem Cells/cytology/*immunology/metabolism MH - RNA, Messenger/analysis MH - Umbilical Cord/cytology/immunology/metabolism EDAT- 2010/03/09 06:00 MHDA- 2010/06/10 06:00 CRDT- 2010/03/09 06:00 PHST- 2009/11/06 00:00 [received] PHST- 2010/01/21 00:00 [revised] PHST- 2010/01/27 00:00 [accepted] PHST- 2010/03/09 06:00 [entrez] PHST- 2010/03/09 06:00 [pubmed] PHST- 2010/06/10 06:00 [medline] AID - S1521-6616(10)00036-7 [pii] AID - 10.1016/j.clim.2010.01.015 [doi] PST - ppublish SO - Clin Immunol. 2010 Jun;135(3):448-58. doi: 10.1016/j.clim.2010.01.015. Epub 2010 Mar 5.