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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0021745,
umls-concept:C0086418,
umls-concept:C0162638,
umls-concept:C0185117,
umls-concept:C0245662,
umls-concept:C0913626,
umls-concept:C1257792,
umls-concept:C1539477,
umls-concept:C1705955,
umls-concept:C2911684
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pubmed:issue |
4
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pubmed:dateCreated |
2002-10-7
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pubmed:abstractText |
We have examined the effects of interferon (IFN)-gamma on expression and function of CD95 (APO-1/Fas) and associated proteins in cultured human umbilical vein and dermal microvascular endothelial cells (HUVEC and HDMEC, respectively). Unstimulated cells express only low levels of CD95; IFN-gamma produces a time- and concentration-dependent increase of CD95 in both cell types at the mRNA and cell surface protein levels. IFN-gamma also produces an increase in expression of pro-caspase-8 (FLICE/MACH) but does not significantly change expression of either Fas-associated death domain (FADD) protein or cellular FLICE inhibitory protein (cFLIP), other proteins associated with the CD95 death-inducing signaling complex (DISC). Neither resting nor IFN-gamma-treated EC express detectable CD95L mRNA or protein. Untreated HUVEC and HDMEC show minimal apoptosis when transduced to express CD95L. Treatment of CD95L-transduced cells with IFN-gamma causes apoptosis within 24 to 36 hours that can be blocked by antagonistic anti-CD95 antibody or by the caspase-inhibitory peptide zVAD-FMK. The extent of apoptosis is increased by co-treatment with either the protein synthesis inhibitor cycloheximide or the phosphatidylinositol 3-kinase inhibitor LY294002. Untransduced HUVEC treated with IFN-gamma also undergo CD95-initiated apoptosis when mixed with CD95L-transduced HUVEC or when incubated with pharmacologically activated cytolytic T lymphocytes. Overexpression of CD95 in HUVEC confers sensitivity to CD95L in the absence of IFN-gamma-treatment. We conclude that IFN-gamma induces sensitivity of endothelium to CD95L-mediated apoptosis, and that this response may result from increased expression of CD95 and/or pro-caspase-8.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/12368221-10358762,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12368221-10500109,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12368221-10646607,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12368221-10669625,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12368221-10690403,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12368221-10779771,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12368221-10894163,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/12368221-11048730,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/12368221-9485186,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12368221-9501089,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12368221-9546786,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/12368221-9915703
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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/Amino Acid Chloromethyl Ketones,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD95,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP9 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 8,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/FASLG protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Fas Ligand Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/benzyloxycarbonylvalyl-alanyl-aspart...
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0002-9440
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
161
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pubmed:owner |
NLM
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