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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1998-1-23
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0007-1048
pubmed:author
pubmed:issnType
Print
pubmed:volume
99
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
481-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Induction of nitric oxide synthase is involved in the mechanism of Fas-mediated apoptosis in haemopoietic cells.
pubmed:affiliation
Division of Haematology, Federico II University Medical School, Naples, Italy.
pubmed:publicationType
Journal Article