Document Detail


Inflammatory cytokine induced regulation of superoxide dismutase 3 expression by human mesenchymal stem cells.
MedLine Citation:
PMID:  20683679     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Kevin Kemp; Elizabeth Gray; Elizabeth Mallam; Neil Scolding; Alastair Wilkins
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Stem cell reviews     Volume:  6     ISSN:  1558-6804     ISO Abbreviation:  Stem Cell Rev     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-10-04     Completed Date:  2011-01-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101255952     Medline TA:  Stem Cell Rev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  548-59     Citation Subset:  IM    
Affiliation:
Multiple Sclerosis and Stem Cell Group, Institute of Clinical Neurosciences, Clinical Sciences North Bristol, University of Bristol, Bristol, UK. kevin.kemp@bristol.ac.uk
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MeSH Terms
Descriptor/Qualifier:
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:
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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