The FASEB journal, 2014-09, Vol.28 (9), p.3856-3866
2014
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Details
- Autor(en) / Beteiligte
- Titel
- Stimulation of mesenchymal stromal cells (MSCs) via TLR3 reveals a novel mechanism of autocrine priming
- Ist Teil von
- The FASEB journal, 2014-09, Vol.28 (9), p.3856-3866
- Ort / Verlag
- United States: The Federation of American Societies for Experimental Biology
- Erscheinungsjahr
- 2014
- Quelle
- Wiley Online Library - AutoHoldings Journals
- Beschreibungen/Notizen
- Mesenchymal stem/stromal cells (MSCs) are emerging as important regulators of innate and adaptive immunity. In this context, both proinflammatory and anti‐inflammatory effects have been described for MSCs. The mechanisms mediating this functional plasticity are poorly characterized at present. Here, we investigated the inflammatory responses of MSCs isolated from human nasal mucosa (nmMSCs) upon challenge with different Toll‐like receptor (TLR) ligands. We found that TLR3 ligands induced the strongest release of both proinflammatory cytokines [interleukin (IL)‐6 and IL‐8] and type I interferon by nmMSCs compared with other TLR ligands. Notably, TLR3 ligands triggered a biphasic cytokine response, with an early peak of type I interferon at 4 h poststimulation and a late release of proinflammatory cytokines at 24 h poststimulation. While the early interferon response was subject to direct stimulation, the proinflammatory response was regulated by factors released during the early cytokine response, which subsequently enhanced sensitivity to TLR3 ligation and amplified the production of IL‐6 and IL‐8 but not that of interferon. Taken together, our findings indicate that TLR3 ligands polarize the inflammatory phenotype of MSCs in a time‐dependent manner. Thus, our study proposes a novel model that helps to explain the strikingly dichotomous functionality of MSCs in inflammation and immunoregulation.—Dumitru, C. A., Hemeda, H., Jakob, M., Lang, S., Brandau, S. Stimulation of mesenchymal stromal cells (MSCs) via TLR3 reveals a novel mechanism of autocrine priming. FASEB J. 28, 3856‐3866 (2014). www.fasebj.org
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0892-6638eISSN: 1530-6860DOI: 10.1096/fj.14-250159Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5395723
- Format
- –
- Schlagworte
- Adult, Aged, Autocrine Communication, biphasic cytokine response, Blotting, Western, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Female, Fluorescent Antibody Technique, functional polarization, Humans, Inflammation - immunology, Inflammation - metabolism, Inflammation - pathology, Inflammation Mediators - metabolism, interferon type I, Interferon-gamma - metabolism, Interleukin-6 - genetics, Interleukin-6 - metabolism, Interleukin-8 - genetics, Interleukin-8 - metabolism, Lipopolysaccharides - pharmacology, Male, Mesenchymal Stromal Cells - cytology, Mesenchymal Stromal Cells - drug effects, Mesenchymal Stromal Cells - immunology, Mesenchymal Stromal Cells - metabolism, Middle Aged, Nasal Mucosa - cytology, Nasal Mucosa - drug effects, Nasal Mucosa - immunology, Nasal Mucosa - metabolism, Poly I:C, proinflammatory cytokines, Real-Time Polymerase Chain Reaction, Research Communications, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger - genetics, Toll-Like Receptor 3 - agonists, Toll-Like Receptor 3 - genetics, Toll-Like Receptor 3 - metabolism