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Mouse Bone Marrow-Derived Mesenchymal Stromal Cells Turn Activated Macrophages into a Regulatory-Like Profile

In recent years it has become clear that the therapeutic properties of bone marrow-derived mesenchymal stromal cells (MSC) are related not only to their ability to differentiate into different lineages but also to their capacity to suppress the immune response. We here studied the influence of MSC o...

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Autores principales: Maggini, Julian, Mirkin, Gerardo, Bognanni, Ianina, Holmberg, Josefina, Piazzón, Isabel M., Nepomnaschy, Irene, Costa, Héctor, Cañones, Cristian, Raiden, Silvina, Vermeulen, Mónica, Geffner, Jorge R.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2821929/
https://www.ncbi.nlm.nih.gov/pubmed/20169081
http://dx.doi.org/10.1371/journal.pone.0009252
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author Maggini, Julian
Mirkin, Gerardo
Bognanni, Ianina
Holmberg, Josefina
Piazzón, Isabel M.
Nepomnaschy, Irene
Costa, Héctor
Cañones, Cristian
Raiden, Silvina
Vermeulen, Mónica
Geffner, Jorge R.
author_facet Maggini, Julian
Mirkin, Gerardo
Bognanni, Ianina
Holmberg, Josefina
Piazzón, Isabel M.
Nepomnaschy, Irene
Costa, Héctor
Cañones, Cristian
Raiden, Silvina
Vermeulen, Mónica
Geffner, Jorge R.
author_sort Maggini, Julian
collection PubMed
description In recent years it has become clear that the therapeutic properties of bone marrow-derived mesenchymal stromal cells (MSC) are related not only to their ability to differentiate into different lineages but also to their capacity to suppress the immune response. We here studied the influence of MSC on macrophage function. Using mouse thioglycolate-elicited peritoneal macrophages (M) stimulated with LPS, we found that MSC markedly suppressed the production of the inflammatory cytokines TNF-α, IL-6, IL-12p70 and interferon-γ while increased the production of IL-10 and IL-12p40. Similar results were observed using supernatants from MSC suggesting that factor(s) constitutively released by MSC are involved. Supporting a role for PGE(2) we observed that acetylsalicylic acid impaired the ability of MSC to inhibit the production of inflammatory cytokines and to stimulate the production of IL-10 by LPS-stimulated M. Moreover, we found that MSC constitutively produce PGE2 at levels able to inhibit the production of TNF-α and IL-6 by activated M. MSC also inhibited the up-regulation of CD86 and MHC class II in LPS-stimulated M impairing their ability to activate antigen-specific T CD4+ cells. On the other hand, they stimulated the uptake of apoptotic thymocytes by M. Of note, MSC turned M into cells highly susceptible to infection with the parasite Trypanosoma cruzi increasing more than 5-fold the rate of M infection. Using a model of inflammation triggered by s.c. implantation of glass cylinders, we found that MSC stimulated the recruitment of macrophages which showed a low expression of CD86 and the MHC class II molecule Ia(b) and a high ability to produce IL-10 and IL-12p40, but not IL-12 p70. In summary, our results suggest that MSC switch M into a regulatory profile characterized by a low ability to produce inflammatory cytokines, a high ability to phagocyte apoptotic cells, and a marked increase in their susceptibility to infection by intracellular pathogens.
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spelling pubmed-28219292010-02-19 Mouse Bone Marrow-Derived Mesenchymal Stromal Cells Turn Activated Macrophages into a Regulatory-Like Profile Maggini, Julian Mirkin, Gerardo Bognanni, Ianina Holmberg, Josefina Piazzón, Isabel M. Nepomnaschy, Irene Costa, Héctor Cañones, Cristian Raiden, Silvina Vermeulen, Mónica Geffner, Jorge R. PLoS One Research Article In recent years it has become clear that the therapeutic properties of bone marrow-derived mesenchymal stromal cells (MSC) are related not only to their ability to differentiate into different lineages but also to their capacity to suppress the immune response. We here studied the influence of MSC on macrophage function. Using mouse thioglycolate-elicited peritoneal macrophages (M) stimulated with LPS, we found that MSC markedly suppressed the production of the inflammatory cytokines TNF-α, IL-6, IL-12p70 and interferon-γ while increased the production of IL-10 and IL-12p40. Similar results were observed using supernatants from MSC suggesting that factor(s) constitutively released by MSC are involved. Supporting a role for PGE(2) we observed that acetylsalicylic acid impaired the ability of MSC to inhibit the production of inflammatory cytokines and to stimulate the production of IL-10 by LPS-stimulated M. Moreover, we found that MSC constitutively produce PGE2 at levels able to inhibit the production of TNF-α and IL-6 by activated M. MSC also inhibited the up-regulation of CD86 and MHC class II in LPS-stimulated M impairing their ability to activate antigen-specific T CD4+ cells. On the other hand, they stimulated the uptake of apoptotic thymocytes by M. Of note, MSC turned M into cells highly susceptible to infection with the parasite Trypanosoma cruzi increasing more than 5-fold the rate of M infection. Using a model of inflammation triggered by s.c. implantation of glass cylinders, we found that MSC stimulated the recruitment of macrophages which showed a low expression of CD86 and the MHC class II molecule Ia(b) and a high ability to produce IL-10 and IL-12p40, but not IL-12 p70. In summary, our results suggest that MSC switch M into a regulatory profile characterized by a low ability to produce inflammatory cytokines, a high ability to phagocyte apoptotic cells, and a marked increase in their susceptibility to infection by intracellular pathogens. Public Library of Science 2010-02-16 /pmc/articles/PMC2821929/ /pubmed/20169081 http://dx.doi.org/10.1371/journal.pone.0009252 Text en Maggini et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Maggini, Julian
Mirkin, Gerardo
Bognanni, Ianina
Holmberg, Josefina
Piazzón, Isabel M.
Nepomnaschy, Irene
Costa, Héctor
Cañones, Cristian
Raiden, Silvina
Vermeulen, Mónica
Geffner, Jorge R.
Mouse Bone Marrow-Derived Mesenchymal Stromal Cells Turn Activated Macrophages into a Regulatory-Like Profile
title Mouse Bone Marrow-Derived Mesenchymal Stromal Cells Turn Activated Macrophages into a Regulatory-Like Profile
title_full Mouse Bone Marrow-Derived Mesenchymal Stromal Cells Turn Activated Macrophages into a Regulatory-Like Profile
title_fullStr Mouse Bone Marrow-Derived Mesenchymal Stromal Cells Turn Activated Macrophages into a Regulatory-Like Profile
title_full_unstemmed Mouse Bone Marrow-Derived Mesenchymal Stromal Cells Turn Activated Macrophages into a Regulatory-Like Profile
title_short Mouse Bone Marrow-Derived Mesenchymal Stromal Cells Turn Activated Macrophages into a Regulatory-Like Profile
title_sort mouse bone marrow-derived mesenchymal stromal cells turn activated macrophages into a regulatory-like profile
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2821929/
https://www.ncbi.nlm.nih.gov/pubmed/20169081
http://dx.doi.org/10.1371/journal.pone.0009252
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