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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
1998-1-23
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pubmed:abstractText |
Induction of nitric oxide synthase (iNOS) and production of the toxic metabolite nitric oxide (NO) is one of the interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) regulated effector mechanisms that can lead to apoptosis of haemopoietic progenitor cells. Fas-receptor (Fas-R) expression can be stimulated by IFN-gamma and TNF-alpha. Transactivation of iNOS, and possibly Fas-R promoters, by interferon regulatory factor-1 expressed in response to IFN-gamma may be a part of the iNOS transduction pathway. We investigated whether the effects of Fas-R triggering in haemopoietic cells were mediated by NO. On Western blotting, we observed that Fas-receptor agonist, monoclonal antibody CH11. enhanced expression of iNOS. As shown by the reverse transcription polymerase chain reaction. CH11 also induced iNOS mRNA expression in purified CD34+ cells. To determine whether NO was involved in Fas-mediated apoptosis we inhibited iNOS-catalysed production of NO using anti-sense (AS) oligodeoxynucleotides (ODN) directed against iNOS mRNA. After culture of haemopoietic cells in the presence of AS-ODN, iNOS expression decreased and was no longer enhanced by Fas. This effect was associated with the prevention of Fas-mediated apoptosis, as determined by a DNA fragmentation and terminal deoxynucleotidyl transferase staining. In colony assays, specific AS-oligonucleotides prevented FAS-mediated inhibition of colony formation by total bone marrow and CD34+ progenitor cells. Our data suggest that the inhibitory effects of Fas, including induction of apoptosis, are mediated by effector mechanisms that may be similar to those described for IFN-gamma and TNF-alpha.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/FASLG protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Fas Ligand Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides, Antisense,
http://linkedlifedata.com/resource/pubmed/chemical/omega-N-Methylarginine
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0007-1048
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
99
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
481-9
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9401054-Apoptosis,
pubmed-meshheading:9401054-Bone Marrow Cells,
pubmed-meshheading:9401054-Fas Ligand Protein,
pubmed-meshheading:9401054-Hematopoietic Stem Cells,
pubmed-meshheading:9401054-Humans,
pubmed-meshheading:9401054-Membrane Glycoproteins,
pubmed-meshheading:9401054-Nitric Oxide,
pubmed-meshheading:9401054-Nitric Oxide Synthase,
pubmed-meshheading:9401054-Oligonucleotides, Antisense,
pubmed-meshheading:9401054-omega-N-Methylarginine
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pubmed:year |
1997
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pubmed:articleTitle |
Induction of nitric oxide synthase is involved in the mechanism of Fas-mediated apoptosis in haemopoietic cells.
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pubmed:affiliation |
Division of Haematology, Federico II University Medical School, Naples, Italy.
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pubmed:publicationType |
Journal Article
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