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Interaction with Mesenchymal Stem Cells Provokes Natural Killer Cells for Enhanced IL-12/IL-18-Induced Interferon-Gamma Secretion

Tissue injury induces an inflammatory response accompanied by the recruitment of immune cells and of mesenchymal stem cells (MSC) that contribute to tissue regeneration. After stimulation with interleukin- (IL-) 12 and IL-18 natural killer (NK) cells secrete the proinflammatory cytokine interferon-...

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Autores principales: Thomas, Heike, Jäger, Marcus, Mauel, Katharina, Brandau, Sven, Lask, Sara, Flohé, Stefanie B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4021755/
https://www.ncbi.nlm.nih.gov/pubmed/24876666
http://dx.doi.org/10.1155/2014/143463
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author Thomas, Heike
Jäger, Marcus
Mauel, Katharina
Brandau, Sven
Lask, Sara
Flohé, Stefanie B.
author_facet Thomas, Heike
Jäger, Marcus
Mauel, Katharina
Brandau, Sven
Lask, Sara
Flohé, Stefanie B.
author_sort Thomas, Heike
collection PubMed
description Tissue injury induces an inflammatory response accompanied by the recruitment of immune cells and of mesenchymal stem cells (MSC) that contribute to tissue regeneration. After stimulation with interleukin- (IL-) 12 and IL-18 natural killer (NK) cells secrete the proinflammatory cytokine interferon- (IFN-) γ. IFN-γ plays a crucial role in the defense against infections and modulates tissue regeneration. In consideration of close proximity of NK cells and MSC at the site of injury we investigated if MSC could influence the ability of NK-cells to produce IFN-γ. Coculture experiments were performed with bone marrow-derived human MSC and human NK cells. MSC enhanced the ability of IL-12/IL-18-stimulated NK cells to secrete IFN-γ in a dose-dependent manner. This activation of NK cells was dependent on cell-cell contact as well as on soluble factors. The increased IFN-γ secretion from NK cells after contact with MSC correlated with an increased level of intracellular IFN-γ. Alterations in the IL-12 signaling pathway including an increased expression of the IL-12β1 receptor subunit and an increased phosphorylation of signal transducer and activator of transcription 4 (STAT4) could be observed. In conclusion, MSC enhance the IFN-γ release from NK cells which might improve the defense against infections at the site of injury but additionally might affect tissue regeneration.
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spelling pubmed-40217552014-05-29 Interaction with Mesenchymal Stem Cells Provokes Natural Killer Cells for Enhanced IL-12/IL-18-Induced Interferon-Gamma Secretion Thomas, Heike Jäger, Marcus Mauel, Katharina Brandau, Sven Lask, Sara Flohé, Stefanie B. Mediators Inflamm Research Article Tissue injury induces an inflammatory response accompanied by the recruitment of immune cells and of mesenchymal stem cells (MSC) that contribute to tissue regeneration. After stimulation with interleukin- (IL-) 12 and IL-18 natural killer (NK) cells secrete the proinflammatory cytokine interferon- (IFN-) γ. IFN-γ plays a crucial role in the defense against infections and modulates tissue regeneration. In consideration of close proximity of NK cells and MSC at the site of injury we investigated if MSC could influence the ability of NK-cells to produce IFN-γ. Coculture experiments were performed with bone marrow-derived human MSC and human NK cells. MSC enhanced the ability of IL-12/IL-18-stimulated NK cells to secrete IFN-γ in a dose-dependent manner. This activation of NK cells was dependent on cell-cell contact as well as on soluble factors. The increased IFN-γ secretion from NK cells after contact with MSC correlated with an increased level of intracellular IFN-γ. Alterations in the IL-12 signaling pathway including an increased expression of the IL-12β1 receptor subunit and an increased phosphorylation of signal transducer and activator of transcription 4 (STAT4) could be observed. In conclusion, MSC enhance the IFN-γ release from NK cells which might improve the defense against infections at the site of injury but additionally might affect tissue regeneration. Hindawi Publishing Corporation 2014 2014-04-30 /pmc/articles/PMC4021755/ /pubmed/24876666 http://dx.doi.org/10.1155/2014/143463 Text en Copyright © 2014 Heike Thomas et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Thomas, Heike
Jäger, Marcus
Mauel, Katharina
Brandau, Sven
Lask, Sara
Flohé, Stefanie B.
Interaction with Mesenchymal Stem Cells Provokes Natural Killer Cells for Enhanced IL-12/IL-18-Induced Interferon-Gamma Secretion
title Interaction with Mesenchymal Stem Cells Provokes Natural Killer Cells for Enhanced IL-12/IL-18-Induced Interferon-Gamma Secretion
title_full Interaction with Mesenchymal Stem Cells Provokes Natural Killer Cells for Enhanced IL-12/IL-18-Induced Interferon-Gamma Secretion
title_fullStr Interaction with Mesenchymal Stem Cells Provokes Natural Killer Cells for Enhanced IL-12/IL-18-Induced Interferon-Gamma Secretion
title_full_unstemmed Interaction with Mesenchymal Stem Cells Provokes Natural Killer Cells for Enhanced IL-12/IL-18-Induced Interferon-Gamma Secretion
title_short Interaction with Mesenchymal Stem Cells Provokes Natural Killer Cells for Enhanced IL-12/IL-18-Induced Interferon-Gamma Secretion
title_sort interaction with mesenchymal stem cells provokes natural killer cells for enhanced il-12/il-18-induced interferon-gamma secretion
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4021755/
https://www.ncbi.nlm.nih.gov/pubmed/24876666
http://dx.doi.org/10.1155/2014/143463
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