Source:http://linkedlifedata.com/resource/pubmed/id/10390188
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
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pubmed:dateCreated |
1999-7-16
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pubmed:abstractText |
In previous studies, we have demonstrated that the inhibitory effects of tumor necrosis factor (TNF) and interleukin (IL)-1 on human erythroid colony formation are indirect and mediated by beta and gamma interferon (IFN), respectively, which act directly upon erythroid colony forming units (CFU-E). The in vitro inhibitory effect of gammaIFN but not betaIFN is reversed by exposure to high concentrations of recombinant human (rh) erythropoietin (EPO). Ceramide, a product of sphingomyelin hydrolysis, is a known mediator of apoptotic effects of TNF, IL-1, and gammaIFN. In this report, the effects of ceramide on CFU-E colony formation and its implication in the model described above are evaluated. Endogenous ceramide produced by exposure to bacterial sphingomyelinase (0.2-2.0 U/mL) and exogenous cell-permeable ceramide (C2-ceramide; 5 and 10 mM) significantly inhibited bone marrow CFU-E colony formation. This effect was reversed by the ceramide antagonist sphingosine-1-phosphate (S-1-P). Inhibition of CFU-E by rhgammaIFN, but not rhbetaIFN, was significantly reversed by S-1-P. rhEPO 10 U/mL reversed CFU-E inhibition by C2-ceramide 10 mM. Exposure of marrow cells to rhgammaIFN led to a 57% increase in ceramide content. The present study demonstrates that colony formation by human CFU-E is inhibited by endogenous and exogenous ceramide, and that inhibition by rhgammaIFN can be reversed by the ceramide antagonist S-1-P. Inhibition of CFU-E colony formation by ceramide and by are both reversed by high concentrations of rhEPO. These findings strongly suggest that ceramide mediates inhibition of human CFU-E colony formation by gammaIFN.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD95,
http://linkedlifedata.com/resource/pubmed/chemical/Ceramides,
http://linkedlifedata.com/resource/pubmed/chemical/Erythropoietin,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-beta,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Lysophospholipids,
http://linkedlifedata.com/resource/pubmed/chemical/N-acetylsphingosine,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Sphingomyelin Phosphodiesterase,
http://linkedlifedata.com/resource/pubmed/chemical/Sphingosine,
http://linkedlifedata.com/resource/pubmed/chemical/dihydroceramide,
http://linkedlifedata.com/resource/pubmed/chemical/sphingosine 1-phosphate
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0301-472X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
27
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1133-8
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:10390188-Antigens, CD95,
pubmed-meshheading:10390188-Apoptosis,
pubmed-meshheading:10390188-Ceramides,
pubmed-meshheading:10390188-Colony-Forming Units Assay,
pubmed-meshheading:10390188-Depression, Chemical,
pubmed-meshheading:10390188-Erythroid Precursor Cells,
pubmed-meshheading:10390188-Erythropoiesis,
pubmed-meshheading:10390188-Erythropoietin,
pubmed-meshheading:10390188-Humans,
pubmed-meshheading:10390188-Interferon-beta,
pubmed-meshheading:10390188-Interferon-gamma,
pubmed-meshheading:10390188-Lysophospholipids,
pubmed-meshheading:10390188-Recombinant Proteins,
pubmed-meshheading:10390188-Sphingomyelin Phosphodiesterase,
pubmed-meshheading:10390188-Sphingosine
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pubmed:year |
1999
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pubmed:articleTitle |
Inhibition of human erythroid colony formation by ceramide.
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pubmed:affiliation |
Department of Internal Medicine, Department of Veterans Affairs Medical Center and the University of Cincinnati College of Medicine, OH, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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