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Mediators of Inflammation
Volume 2014, Article ID 143463, 11 pages
http://dx.doi.org/10.1155/2014/143463
Research Article

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

1Orthopedic Research, Department of Orthopedics, University Hospital Essen, University Duisburg-Essen, Virchowstraße 171, 45147 Essen, Germany
2Surgical Research, Department of Trauma Surgery, University Hospital Essen, University Duisburg-Essen, Virchowstraße 171, 45147 Essen, Germany
3Department of Otolaryngology, University Hospital Essen, University Duisburg-Essen, Virchowstraße 171, 45147 Essen, Germany

Received 23 January 2014; Revised 2 April 2014; Accepted 8 April 2014; Published 30 April 2014

Academic Editor: Jonathan Peake

Copyright © 2014 Heike Thomas et al. 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.

Abstract

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-12 1 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.