PMID- 25204503 OWN - NLM STAT- MEDLINE DCOM- 20150225 LR - 20181202 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 452 IP - 3 DP - 2014 Sep 26 TI - Inhibition of DNA methylation enhances HLA-G expression in human mesenchymal stem cells. PG - 753-9 LID - S0006-291X(14)01596-4 [pii] LID - 10.1016/j.bbrc.2014.08.152 [doi] AB - Mesenchymal stem cells (MSCs) are immunosuppressive multipotent cells under investigation for potential therapeutic applications in regenerative medicine and prevention of graft-versus-host disease. Human leukocyte antigen (HLA)-G contributes to the immunomodulatory properties of MSCs. HLA-G expression in MSCs is very low and diminishes during in vitro expansion. Epigenetic regulation activates HLA-G expression in some cancer cell lines but not in MSCs. In the present study, adipose- and bone marrow-derived MSCs were exposed to the DNA demethylating agent 5-aza-2-deoxycytidine (5-aza-dC) and histone deacetylase inhibitor valproic acid (VPA) and HLA-G mRNA levels assessed using semi-quantitative reverse-transcription PCR. Exposure to 5-aza-dC resulted in HLA-G1 and -G3 upregulation in both early and late passage MSCs. VPA treatment did not induce HLA-G expression in both bone marrow and adipose derived MSCs. Our results provide the first evidence that HLA-G3 could be expressed in MSCs and that methylation-mediated repression is partly responsible for the observed low levels of HLA-G expression in MSCs. Our findings provide insight that treatment of MSCs with specific epigenetic regulatory modulators may improve their immunoregulatory capability for therapeutic applications. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Teklemariam, Takele AU - Teklemariam T AD - Escape Therapeutics, Inc., San Jose, CA, United States. FAU - Purandare, Bhamini AU - Purandare B AD - San Jose State University, San Jose, CA, United States. FAU - Zhao, Longmei AU - Zhao L AD - Escape Therapeutics, Inc., San Jose, CA, United States. FAU - Hantash, Basil M AU - Hantash BM AD - Escape Therapeutics, Inc., San Jose, CA, United States. Electronic address: basil@escapetherapeutics.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140906 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (HLA-G Antigens) RN - 0 (RNA, Messenger) RN - 614OI1Z5WI (Valproic Acid) RN - 776B62CQ27 (Decitabine) RN - M801H13NRU (Azacitidine) SB - IM MH - Adipose Tissue/cytology/drug effects/metabolism MH - Azacitidine/analogs & derivatives/pharmacology MH - Bone Marrow Cells/cytology/drug effects/metabolism MH - DNA Methylation/drug effects MH - Decitabine MH - *Epigenesis, Genetic MH - HLA-G Antigens/*genetics/metabolism MH - Humans MH - Mesenchymal Stem Cells/cytology/*drug effects/metabolism MH - Primary Cell Culture MH - RNA, Messenger/*genetics/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Signal Transduction MH - Valproic Acid/pharmacology OTO - NOTNLM OT - 5-aza-2-deoxycytidine OT - Epigenetic regulation OT - HLA-G OT - Immunomodulation OT - Mesenchymal stem cells OT - Valproic acid EDAT- 2014/09/11 06:00 MHDA- 2015/02/26 06:00 CRDT- 2014/09/11 06:00 PHST- 2014/08/26 00:00 [received] PHST- 2014/08/28 00:00 [accepted] PHST- 2014/09/11 06:00 [entrez] PHST- 2014/09/11 06:00 [pubmed] PHST- 2015/02/26 06:00 [medline] AID - S0006-291X(14)01596-4 [pii] AID - 10.1016/j.bbrc.2014.08.152 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2014 Sep 26;452(3):753-9. doi: 10.1016/j.bbrc.2014.08.152. Epub 2014 Sep 6.