Cargando…
DNA methyltransferase inhibition accelerates the immunomodulation and migration of human mesenchymal stem cells
DNA methyltransferase (DNMT) inhibitors regulate target gene expression through epigenetic modifications, and these compounds have primarily been studied for cancer therapy or reprogramming. However, the effect of DNMT inhibitors on the immunomodulatory capacity of human mesenchymal stem cells (hMSC...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306122/ https://www.ncbi.nlm.nih.gov/pubmed/25620445 http://dx.doi.org/10.1038/srep08020 |
_version_ | 1782354284951633920 |
---|---|
author | Lee, Seunghee Kim, Hyung-Sik Roh, Kyoung-Hwan Lee, Byung-Chul Shin, Tae-Hoon Yoo, Ju-Mi Kim, Yu-Lee Yu, Kyung-Rok Kang, Kyung-Sun Seo, Kwang-Won |
author_facet | Lee, Seunghee Kim, Hyung-Sik Roh, Kyoung-Hwan Lee, Byung-Chul Shin, Tae-Hoon Yoo, Ju-Mi Kim, Yu-Lee Yu, Kyung-Rok Kang, Kyung-Sun Seo, Kwang-Won |
author_sort | Lee, Seunghee |
collection | PubMed |
description | DNA methyltransferase (DNMT) inhibitors regulate target gene expression through epigenetic modifications, and these compounds have primarily been studied for cancer therapy or reprogramming. However, the effect of DNMT inhibitors on the immunomodulatory capacity of human mesenchymal stem cells (hMSCs) has not been investigated. In the present study, we treated hMSCs with 5-azacytidine (5-aza), a DNMT inhibitor, and confirmed that the inhibitory effects on mononuclear cell proliferation and cell migration toward activated T cells were increased. To identify the immunomodulatory factors stimulated through 5-aza treatment, we investigated the changes in promoter methylation patterns using methylation arrays and observed that the promoters of immunomodulatory factors, COX2 and PTGES, and migration-related factors, CXCR2 and CXCR4, were hypomethylated after 5-aza treatment. In addition, we observed that the COX2-PGE(2) pathway is one of the main pathways for the enhanced immunosuppressive activity of hMSCs through 5-aza treatment. We also determined that the migration of hMSCs toward ligands for CXCR2/CXCR4 was increased after 5-aza treatment. Moreover, using an experimental colitis model, we showed that 5-aza pre-treatment could enhance the therapeutic effect of MSCs against immune-related diseases. |
format | Online Article Text |
id | pubmed-4306122 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-43061222015-02-05 DNA methyltransferase inhibition accelerates the immunomodulation and migration of human mesenchymal stem cells Lee, Seunghee Kim, Hyung-Sik Roh, Kyoung-Hwan Lee, Byung-Chul Shin, Tae-Hoon Yoo, Ju-Mi Kim, Yu-Lee Yu, Kyung-Rok Kang, Kyung-Sun Seo, Kwang-Won Sci Rep Article DNA methyltransferase (DNMT) inhibitors regulate target gene expression through epigenetic modifications, and these compounds have primarily been studied for cancer therapy or reprogramming. However, the effect of DNMT inhibitors on the immunomodulatory capacity of human mesenchymal stem cells (hMSCs) has not been investigated. In the present study, we treated hMSCs with 5-azacytidine (5-aza), a DNMT inhibitor, and confirmed that the inhibitory effects on mononuclear cell proliferation and cell migration toward activated T cells were increased. To identify the immunomodulatory factors stimulated through 5-aza treatment, we investigated the changes in promoter methylation patterns using methylation arrays and observed that the promoters of immunomodulatory factors, COX2 and PTGES, and migration-related factors, CXCR2 and CXCR4, were hypomethylated after 5-aza treatment. In addition, we observed that the COX2-PGE(2) pathway is one of the main pathways for the enhanced immunosuppressive activity of hMSCs through 5-aza treatment. We also determined that the migration of hMSCs toward ligands for CXCR2/CXCR4 was increased after 5-aza treatment. Moreover, using an experimental colitis model, we showed that 5-aza pre-treatment could enhance the therapeutic effect of MSCs against immune-related diseases. Nature Publishing Group 2015-01-26 /pmc/articles/PMC4306122/ /pubmed/25620445 http://dx.doi.org/10.1038/srep08020 Text en Copyright © 2015, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | Article Lee, Seunghee Kim, Hyung-Sik Roh, Kyoung-Hwan Lee, Byung-Chul Shin, Tae-Hoon Yoo, Ju-Mi Kim, Yu-Lee Yu, Kyung-Rok Kang, Kyung-Sun Seo, Kwang-Won DNA methyltransferase inhibition accelerates the immunomodulation and migration of human mesenchymal stem cells |
title | DNA methyltransferase inhibition accelerates the immunomodulation and migration of human mesenchymal stem cells |
title_full | DNA methyltransferase inhibition accelerates the immunomodulation and migration of human mesenchymal stem cells |
title_fullStr | DNA methyltransferase inhibition accelerates the immunomodulation and migration of human mesenchymal stem cells |
title_full_unstemmed | DNA methyltransferase inhibition accelerates the immunomodulation and migration of human mesenchymal stem cells |
title_short | DNA methyltransferase inhibition accelerates the immunomodulation and migration of human mesenchymal stem cells |
title_sort | dna methyltransferase inhibition accelerates the immunomodulation and migration of human mesenchymal stem cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306122/ https://www.ncbi.nlm.nih.gov/pubmed/25620445 http://dx.doi.org/10.1038/srep08020 |
work_keys_str_mv | AT leeseunghee dnamethyltransferaseinhibitionacceleratestheimmunomodulationandmigrationofhumanmesenchymalstemcells AT kimhyungsik dnamethyltransferaseinhibitionacceleratestheimmunomodulationandmigrationofhumanmesenchymalstemcells AT rohkyounghwan dnamethyltransferaseinhibitionacceleratestheimmunomodulationandmigrationofhumanmesenchymalstemcells AT leebyungchul dnamethyltransferaseinhibitionacceleratestheimmunomodulationandmigrationofhumanmesenchymalstemcells AT shintaehoon dnamethyltransferaseinhibitionacceleratestheimmunomodulationandmigrationofhumanmesenchymalstemcells AT yoojumi dnamethyltransferaseinhibitionacceleratestheimmunomodulationandmigrationofhumanmesenchymalstemcells AT kimyulee dnamethyltransferaseinhibitionacceleratestheimmunomodulationandmigrationofhumanmesenchymalstemcells AT yukyungrok dnamethyltransferaseinhibitionacceleratestheimmunomodulationandmigrationofhumanmesenchymalstemcells AT kangkyungsun dnamethyltransferaseinhibitionacceleratestheimmunomodulationandmigrationofhumanmesenchymalstemcells AT seokwangwon dnamethyltransferaseinhibitionacceleratestheimmunomodulationandmigrationofhumanmesenchymalstemcells |