Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1999-7-16
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
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
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0301-472X
pubmed:author
pubmed:issnType
Print
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1133-8
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Inhibition of human erythroid colony formation by ceramide.
pubmed:affiliation
Department of Internal Medicine, Department of Veterans Affairs Medical Center and the University of Cincinnati College of Medicine, OH, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.