TNFa and IL-1ß influence the differentiation and migration of murine MSCs independently of the NF-kB pathway

Hdl Handle:
http://hdl.handle.net/10147/331822
Title:
TNFa and IL-1ß influence the differentiation and migration of murine MSCs independently of the NF-kB pathway
Authors:
Sullivan, Catherine B; Porter, Ryan M; Evans, Chris H; Ritter, Thomas; Shaw, Georgina; Barry, Frank; Murphy, Josephine M
Citation:
Sullivan CB et al. TNFa and IL-1ß influence the differentiation and migration of murine MSCs independently of the NF-kB pathway. Stem Cell Res & Ther. 2014 Aug 27;5(4):104
Issue Date:
27-Aug-2014
URI:
http://dx.doi.org/10.1186/scrt492; http://hdl.handle.net/10147/331822
Abstract:
Abstract Introduction Mesenchymal stem cells (MSCs) have the ability to repair and regenerate tissue, home to sites of inflammation, and evade the host immune system. As such, they represent an attractive therapy for the treatment of autoimmune inflammatory diseases. However, results from in vivo murine studies in inflammatory arthritis have been conflicting, and this may be due to the genetic background of the MSCs used. It is known that the inflammatory milieu may influence properties of MSCs and that, in the case of human bone marrow-derived MSCs, this may be mediated by the nuclear factor-kappa-B (NF-κB) pathway. We sought to determine whether pro-inflammatory cytokines altered the differentiation and migration capacity of murine MSCs from different mouse strains and whether this was mediated by NF-κB. Methods The differentiation and migration of FVB and BALB/c MSCs were carried out in the presence of varying concentrations of tumor necrosis factor-alpha (TNFα) and interleukin (IL)-1β, and the NF-κB pathway was inhibited in one of two ways: either by transduction of MSCs with an adenoviral vector expressing a super-repressor of NF-κB or by the addition of curcumin to culture media. Results Both BALB/c and FVB MSCs were sensitive to the effect of pro-inflammatory cytokines in vitro. TNFα and IL-1β suppressed BALB/c osteogenesis and adipogenesis and FVB osteogenesis. The migration of both cell types toward media containing fetal bovine serum was augmented by pre-stimulation with either cytokine. In neither cell type were the cytokine effects reversed by abrogation of the NF-κB pathway. Conclusions These data show that murine MSCs from different genetic backgrounds may be influenced by an inflammatory milieu in a manner that is not mediated by NF-κB, as is the case for human MSCs. This is not mediated by NF-κB. These findings are important and should influence how in vivo trials of murine MSCs are interpreted and the future development of pre-clinical studies in inflammatory diseases.
Item Type:
Article
Language:
en
Keywords:
GENETICS
Local subject classification:
INFLAMMATORY DISEASES

Full metadata record

DC FieldValue Language
dc.contributor.authorSullivan, Catherine Ben_GB
dc.contributor.authorPorter, Ryan Men_GB
dc.contributor.authorEvans, Chris Hen_GB
dc.contributor.authorRitter, Thomasen_GB
dc.contributor.authorShaw, Georginaen_GB
dc.contributor.authorBarry, Franken_GB
dc.contributor.authorMurphy, Josephine Men_GB
dc.date.accessioned2014-09-24T11:02:37Z-
dc.date.available2014-09-24T11:02:37Z-
dc.date.issued2014-08-27-
dc.identifier.citationSullivan CB et al. TNFa and IL-1ß influence the differentiation and migration of murine MSCs independently of the NF-kB pathway. Stem Cell Res & Ther. 2014 Aug 27;5(4):104en_GB
dc.identifier.urihttp://dx.doi.org/10.1186/scrt492-
dc.identifier.urihttp://hdl.handle.net/10147/331822-
dc.description.abstractAbstract Introduction Mesenchymal stem cells (MSCs) have the ability to repair and regenerate tissue, home to sites of inflammation, and evade the host immune system. As such, they represent an attractive therapy for the treatment of autoimmune inflammatory diseases. However, results from in vivo murine studies in inflammatory arthritis have been conflicting, and this may be due to the genetic background of the MSCs used. It is known that the inflammatory milieu may influence properties of MSCs and that, in the case of human bone marrow-derived MSCs, this may be mediated by the nuclear factor-kappa-B (NF-κB) pathway. We sought to determine whether pro-inflammatory cytokines altered the differentiation and migration capacity of murine MSCs from different mouse strains and whether this was mediated by NF-κB. Methods The differentiation and migration of FVB and BALB/c MSCs were carried out in the presence of varying concentrations of tumor necrosis factor-alpha (TNFα) and interleukin (IL)-1β, and the NF-κB pathway was inhibited in one of two ways: either by transduction of MSCs with an adenoviral vector expressing a super-repressor of NF-κB or by the addition of curcumin to culture media. Results Both BALB/c and FVB MSCs were sensitive to the effect of pro-inflammatory cytokines in vitro. TNFα and IL-1β suppressed BALB/c osteogenesis and adipogenesis and FVB osteogenesis. The migration of both cell types toward media containing fetal bovine serum was augmented by pre-stimulation with either cytokine. In neither cell type were the cytokine effects reversed by abrogation of the NF-κB pathway. Conclusions These data show that murine MSCs from different genetic backgrounds may be influenced by an inflammatory milieu in a manner that is not mediated by NF-κB, as is the case for human MSCs. This is not mediated by NF-κB. These findings are important and should influence how in vivo trials of murine MSCs are interpreted and the future development of pre-clinical studies in inflammatory diseases.-
dc.language.isoenen
dc.subjectGENETICSen_GB
dc.subject.otherINFLAMMATORY DISEASESen_GB
dc.titleTNFa and IL-1ß influence the differentiation and migration of murine MSCs independently of the NF-kB pathwayen_GB
dc.typeArticleen
dc.language.rfc3066en-
dc.rights.holderCatherine B Sullivan et al.; licensee BioMed Central Ltd.-
dc.description.statusPeer Reviewed-
dc.date.updated2014-09-23T11:03:47Z-
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