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dc.contributor.authorMoen, Siv Helen
dc.contributor.authorWesthrin, Marita
dc.contributor.authorZahoor, Muhammad
dc.contributor.authorNikolai N., Nørgaard
dc.contributor.authorHella, Hanne
dc.contributor.authorStørdal, Berit Fladvad
dc.contributor.authorSundan, Anders
dc.contributor.authorNilsen, Nadra J.
dc.contributor.authorSponaas, Anne-Marit
dc.contributor.authorStandal, Therese
dc.identifier.citationImmunity,Inflammation and Disease 2016nb_NO
dc.description.abstractIntroduction: Mesenchymal stem cells, also called mesenchymal stromal cells, MSCs, have great potential in stem cell therapy partly due to their immunosuppressive properties. How these cells respond to chronic inflammatory stimuli is therefore of importance. Toll-like receptors (TLR)s are innate immune receptors that mediate inflammatory signals in response to infection, stress, and damage. Caspase-8 is involved in activation of NF-kB downstream of TLRs in immune cells. Here we investigated the role of caspase-8 in regulating TLR-induced cytokine production from human bone marrow-derived mesenchymal stromal cells (hBMSCs). Methods: Cytokine expression in hBMCs in response to poly(I:C) and LPS was evaluated by PCR, multiplex cytokine assay, and ELISA. TLR3, TRIF, and caspase-8 were silenced using siRNA. Caspase-8 was also inhibited using a caspase-8 inhibitor, z-IEDT. Results: We found that TLR3 agonist poly(I:C) and TLR4 agonist LPS induced secretion of several pro-inflammatory cytokines in a TLR-dependent manner which required the TLR signaling adaptor molecule TRIF. Further, poly(I:C) reduced the expression of anti-inflammatory cytokines HGF and TGFβ whereas LPS reduced HGF expression only. Notably, caspase-8 was involved in the induction of IL- IL-1β, IL-6, CXCL10, and in the inhibition of HGF and TGFβ. Conclusion: Caspase-8 appears to modulate hBMSCs into gaining a pro-inflammatory phenotype. Therefore, inhibiting caspase-8 in hBMSCs might promote an immunosuppressive phenotype which could be useful in clinical applications to treat inflammatory disorders.nb_NO
dc.publisherWiley Open Accessnb_NO
dc.rightsNavngivelse 3.0 Norge*
dc.titleCaspase-8 regulates the expression of pro- and anti-inflammatory cytokines in human bone marrow-derived mesenchymal stromal cellsnb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.source.journalImmunity,Inflammation and Diseasenb_NO
dc.description.localcode© 2016 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.nb_NO

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Navngivelse 3.0 Norge
Except where otherwise noted, this item's license is described as Navngivelse 3.0 Norge