The interaction between mesenchymal stem cells and steroids during inflammation

Mesenchymal stem cells (MSCs) are believed to exert their regenerative effects through differentiation and modulation of inflammatory responses. However, the relationship between the severity of inflammation and stem cell-mediated tissue repair has not been formally investigated. In this study, we a...

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Main Authors:	Chen, X, Gan, Y, Li, W, Su, J, Zhang, Y, Huang, Y, Roberts, A I, Han, Y, Li, J, Wang, Y, Shi, Y
Format:	Online
Language:	English
Published:	Nature Publishing Group 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4040685/

id	pubmed-4040685
recordtype	oai_dc
spelling	pubmed-40406852014-06-02 The interaction between mesenchymal stem cells and steroids during inflammation Chen, X Gan, Y Li, W Su, J Zhang, Y Huang, Y Roberts, A I Han, Y Li, J Wang, Y Shi, Y Original Article Mesenchymal stem cells (MSCs) are believed to exert their regenerative effects through differentiation and modulation of inflammatory responses. However, the relationship between the severity of inflammation and stem cell-mediated tissue repair has not been formally investigated. In this study, we applied different concentrations of dexamethasone (Dex) to anti-CD3-activated splenocyte cultured with or without MSCs. As expected, Dex exhibited a classical dose-dependent inhibition of T-cell proliferation. Surprisingly, although MSCs also blocked T-cell proliferation, the presence of Dex unexpectedly showed a dose-dependent reversion of T-cell proliferation. This effect of Dex was found to be exerted through interfering STAT1 phosphorylation-prompted expression of inducible nitric oxide synthase (iNOS). Interestingly, inflammation-induced chemokines in MSCs was unaffected. To test the role of inflammation severity in stem cell-mediated tissue repair, we employed mice with carbon tetrachloride-induced advanced liver fibrosis and found that although MSCs alone were effective, concurrent administration of Dex abrogated the therapeutic effects of MSCs on fibrin deposition, serum levels of bilirubin, albumin, and aminotransferases, as well as T-lymphocyte infiltration, especially IFN-γ+CD4+ and IL-17A+CD4+T cells. Likewise, iNOS−/− MSCs, which produce chemokines but not nitric oxide under inflammatory conditions, are ineffective in treating advanced liver fibrosis. Therefore, inflammation has a critical role in MSC-mediated tissue repair. In addition, concomitant application of MSCs with steroids should be avoided. Nature Publishing Group 2014-01 2014-01-23 /pmc/articles/PMC4040685/ /pubmed/24457953 http://dx.doi.org/10.1038/cddis.2013.537 Text en Copyright © 2014 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Chen, X Gan, Y Li, W Su, J Zhang, Y Huang, Y Roberts, A I Han, Y Li, J Wang, Y Shi, Y
spellingShingle	Chen, X Gan, Y Li, W Su, J Zhang, Y Huang, Y Roberts, A I Han, Y Li, J Wang, Y Shi, Y The interaction between mesenchymal stem cells and steroids during inflammation
author_facet	Chen, X Gan, Y Li, W Su, J Zhang, Y Huang, Y Roberts, A I Han, Y Li, J Wang, Y Shi, Y
author_sort	Chen, X
title	The interaction between mesenchymal stem cells and steroids during inflammation
title_short	The interaction between mesenchymal stem cells and steroids during inflammation
title_full	The interaction between mesenchymal stem cells and steroids during inflammation
title_fullStr	The interaction between mesenchymal stem cells and steroids during inflammation
title_full_unstemmed	The interaction between mesenchymal stem cells and steroids during inflammation
title_sort	interaction between mesenchymal stem cells and steroids during inflammation
description	Mesenchymal stem cells (MSCs) are believed to exert their regenerative effects through differentiation and modulation of inflammatory responses. However, the relationship between the severity of inflammation and stem cell-mediated tissue repair has not been formally investigated. In this study, we applied different concentrations of dexamethasone (Dex) to anti-CD3-activated splenocyte cultured with or without MSCs. As expected, Dex exhibited a classical dose-dependent inhibition of T-cell proliferation. Surprisingly, although MSCs also blocked T-cell proliferation, the presence of Dex unexpectedly showed a dose-dependent reversion of T-cell proliferation. This effect of Dex was found to be exerted through interfering STAT1 phosphorylation-prompted expression of inducible nitric oxide synthase (iNOS). Interestingly, inflammation-induced chemokines in MSCs was unaffected. To test the role of inflammation severity in stem cell-mediated tissue repair, we employed mice with carbon tetrachloride-induced advanced liver fibrosis and found that although MSCs alone were effective, concurrent administration of Dex abrogated the therapeutic effects of MSCs on fibrin deposition, serum levels of bilirubin, albumin, and aminotransferases, as well as T-lymphocyte infiltration, especially IFN-γ+CD4+ and IL-17A+CD4+T cells. Likewise, iNOS−/− MSCs, which produce chemokines but not nitric oxide under inflammatory conditions, are ineffective in treating advanced liver fibrosis. Therefore, inflammation has a critical role in MSC-mediated tissue repair. In addition, concomitant application of MSCs with steroids should be avoided.
publisher	Nature Publishing Group
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4040685/
_version_	1612095154231967744

The interaction between mesenchymal stem cells and steroids during inflammation

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