| Inflammatory cytokine induced regulation of superoxide dismutase 3 expression by human mesenchymal stem cells. | |
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MedLine Citation:
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PMID: 20683679 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Increasing evidence suggests that bone marrow derived-mesenchymal stem cells (MSCs) have neuroprotective properties and a major mechanism of action is through their capacity to secrete a diverse range of potentially neurotrophic or anti-oxidant factors. The recent discovery that MSCs secrete superoxide dismutase 3 (SOD3) may help explain studies in which MSCs have a direct anti-oxidant activity that is conducive to neuroprotection in both in vivo and in vitro. SOD3 attenuates tissue damage and reduces inflammation and may confer neuroprotective effects against nitric oxide-mediated stress to cerebellar neurons; but, its role in relation to central nervous system inflammation and neurodegeneration has not been extensively investigated. Here we have performed a series of experiments showing that SOD3 secretion by human bone marrow-derived MSCs is regulated synergistically by the inflammatory cytokines TNF-alpha and IFN-gamma, rather than through direct exposure to reactive oxygen species. Furthermore, we have shown SOD3 secretion by MSCs is increased by activated microglial cells. We have also shown that MSCs and recombinant SOD are able to increase both neuronal and axonal survival in vitro against nitric oxide or microglial induced damage, with an increased MSC-induced neuroprotective effect evident in the presence of inflammatory cytokines TNF-alpha and IFN-gamma. We have shown MSCs are able to convey these neuroprotective effects through secretion of soluble factors alone and furthermore demonstrated that SOD3 secretion by MSCs is, at least, partially responsible for this phenomenon. SOD3 secretion by MSCs maybe of relevance to treatment strategies for inflammatory disease of the central nervous system. |
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Authors:
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Kevin Kemp; Elizabeth Gray; Elizabeth Mallam; Neil Scolding; Alastair Wilkins |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Stem cell reviews Volume: 6 ISSN: 1558-6804 ISO Abbreviation: Stem Cell Rev Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-10-04 Completed Date: 2011-01-20 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101255952 Medline TA: Stem Cell Rev Country: United States |
Other Details:
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Languages: eng Pagination: 548-59 Citation Subset: IM |
Affiliation:
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Multiple Sclerosis and Stem Cell Group, Institute of Clinical Neurosciences, Clinical Sciences North Bristol, University of Bristol, Bristol, UK. kevin.kemp@bristol.ac.uk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Survival / drug effects Cells, Cultured Cytokines / pharmacology* Drug Synergism Enzyme-Linked Immunosorbent Assay Humans Immunoblotting Immunohistochemistry Interferon-gamma / pharmacology Mesenchymal Stem Cells / drug effects*, metabolism* Neurons / cytology, drug effects Nitric Oxide / pharmacology Polymerase Chain Reaction Rats Superoxide Dismutase / metabolism* Tumor Necrosis Factor-alpha / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Tumor Necrosis Factor-alpha; 10102-43-9/Nitric Oxide; 82115-62-6/Interferon-gamma; EC 1.15.1.1/SOD3 protein, human; EC 1.15.1.1/Superoxide Dismutase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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