title: Interaction with mesenchymal stem cells provokes natural killer cells for enhanced IL-12/IL-18-induced interferon-gamma secretion.
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-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.
authors.affiliation: Orthopedic Research, Department of Orthopedics, University Hospital Essen, University Duisburg-Essen, Virchowstraße 171, 45147 Essen, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Thomas
authors.affiliation: Orthopedic Research, Department of Orthopedics, University Hospital Essen, University Duisburg-Essen, Virchowstraße 171, 45147 Essen, Germany ; Surgical Research, Department of Trauma Surgery, University Hospital Essen, University Duisburg-Essen, Virchowstraße 171, 45147 Essen, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Jäger
authors.affiliation: Orthopedic Research, Department of Orthopedics, University Hospital Essen, University Duisburg-Essen, Virchowstraße 171, 45147 Essen, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Mauel
authors.affiliation: Department of Otolaryngology, University Hospital Essen, University Duisburg-Essen, Virchowstraße 171, 45147 Essen, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Brandau
authors.affiliation: Orthopedic Research, Department of Orthopedics, University Hospital Essen, University Duisburg-Essen, Virchowstraße 171, 45147 Essen, Germany.
authors.forename: Sara
authors.initials: S
authors.lastname: Lask
authors.affiliation: Surgical Research, Department of Trauma Surgery, University Hospital Essen, University Duisburg-Essen, Virchowstraße 171, 45147 Essen, Germany.
authors.forename: Stefanie B
authors.initials: SB
authors.lastname: Flohé
mesh_terms: D002450:Cell Communication; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D007371:Interferon-gamma / Q000378:metabolism*; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism*; D020382:Interleukin-18 / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000166:cytology*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D012038:Regeneration; D050797:STAT4 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C573415:IFNG protein, human; C500879:IL12B protein, human; D053762:Interleukin-12 Subunit p40; D020382:Interleukin-18; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D007371:Interferon-gamma