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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2006-12-27
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pubmed:abstractText |
The molecular mechanisms by which mesenchymal stem cells (MSCs) suppress T-cell proliferation are poorly understood, and whether a soluble factor plays a major role remains controversial. Here we demonstrate that the T-cell-receptor complex is not a target for the suppression, suggesting that downstream signals mediate the suppression. We found that Stat5 phosphorylation in T cells is suppressed in the presence of MSCs and that nitric oxide (NO) is involved in the suppression of Stat5 phosphorylation and T-cell proliferation. The induction of inducible NO synthase (NOS) was readily detected in MSCs but not T cells, and a specific inhibitor of NOS reversed the suppression of Stat5 phosphorylation and T-cell proliferation. This production of NO in the presence of MSCs was mediated by CD4 or CD8 T cells but not by CD19 B cells. Furthermore, inhibitors of prostaglandin synthase or NOS restored the proliferation of T cells, whereas an inhibitor of indoleamine 2,3-dioxygenase and a transforming growth factor-beta-neutralizing antibody had no effect. Finally, MSCs from inducible NOS-/- mice had a reduced ability to suppress T-cell proliferation. Taken together, these results suggest that NO produced by MSCs is one of the major mediators of T-cell suppression by MSCs.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1-methyl-tryptophan,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD19,
http://linkedlifedata.com/resource/pubmed/chemical/Concanavalin A,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Indoleamine-Pyrrole 2,3,-Dioxygenase,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Ionomycin,
http://linkedlifedata.com/resource/pubmed/chemical/NG-Nitroarginine Methyl Ester,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type II,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin-Endoperoxide Synthases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/STAT5 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/Tryptophan
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0006-4971
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
109
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
228-34
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:16985180-Animals,
pubmed-meshheading:16985180-Antigens, CD19,
pubmed-meshheading:16985180-B-Lymphocyte Subsets,
pubmed-meshheading:16985180-CD4-Positive T-Lymphocytes,
pubmed-meshheading:16985180-CD8-Positive T-Lymphocytes,
pubmed-meshheading:16985180-Cell Division,
pubmed-meshheading:16985180-Cell Line,
pubmed-meshheading:16985180-Concanavalin A,
pubmed-meshheading:16985180-Cyclooxygenase Inhibitors,
pubmed-meshheading:16985180-Dinoprostone,
pubmed-meshheading:16985180-Enzyme Induction,
pubmed-meshheading:16985180-HeLa Cells,
pubmed-meshheading:16985180-Humans,
pubmed-meshheading:16985180-Indoleamine-Pyrrole 2,3,-Dioxygenase,
pubmed-meshheading:16985180-Interferon-gamma,
pubmed-meshheading:16985180-Interleukin-2,
pubmed-meshheading:16985180-Ionomycin,
pubmed-meshheading:16985180-Lymphocyte Activation,
pubmed-meshheading:16985180-Macrophages,
pubmed-meshheading:16985180-Mesenchymal Stem Cells,
pubmed-meshheading:16985180-Mice,
pubmed-meshheading:16985180-Mice, Inbred C57BL,
pubmed-meshheading:16985180-Mice, Knockout,
pubmed-meshheading:16985180-NG-Nitroarginine Methyl Ester,
pubmed-meshheading:16985180-Nitric Oxide,
pubmed-meshheading:16985180-Nitric Oxide Synthase Type II,
pubmed-meshheading:16985180-Phosphorylation,
pubmed-meshheading:16985180-Prostaglandin-Endoperoxide Synthases,
pubmed-meshheading:16985180-Protein Processing, Post-Translational,
pubmed-meshheading:16985180-Receptors, Antigen, T-Cell,
pubmed-meshheading:16985180-STAT5 Transcription Factor,
pubmed-meshheading:16985180-Signal Transduction,
pubmed-meshheading:16985180-T-Lymphocyte Subsets,
pubmed-meshheading:16985180-Tetradecanoylphorbol Acetate,
pubmed-meshheading:16985180-Transforming Growth Factor beta,
pubmed-meshheading:16985180-Tryptophan
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pubmed:year |
2007
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pubmed:articleTitle |
Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells.
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pubmed:affiliation |
Division of Hematology, Jichi Medical University, 3311-1 Yakushiji, Tochigi 329-0498, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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