Format:
Online-Ressource
ISSN:
1521-4141
Content:
Abstract: Peripheral blood‐derived monocytes spontaneously undergo apoptosis mediated by Fas‐Fas ligand (FasL) interactions. Activation of monocytes by LPS or TNF‐α prevents spontaneous monocyte apoptosis through an unknown mechanism. Here, we demonstrate that LPS and TNF‐α up‐regulate Flip and suppress spontaneous Fas‐FasL mediated monocyte apoptosis and caspase 8 and 3 activation. Flip was responsible for this protection, since inhibition of Flip by antisense oligonucleotides in the presence of LPS or TNF‐α restored monocyte sensitivity to spontaneous apoptosis. We also investigated whether the PI3K pathway contributes to the suppression of spontaneous monocyte apoptosis mediated by LPS and TNF‐α. Monocytes treated with a reversible PI3K inhibitor (LY294002) displayed enhanced apoptosis, while LPS and TNF‐α partially protected against apoptosis mediated by LY294002. However, direct suppression of Fas‐FasL interactions by addition of neutralizing anti‐FasL antibody did not further suppress LY294002‐induced apoptosis in the presence of LPS or TNF‐α. Collectively, these data demonstrate that LPS or TNF‐α protect monocytes from death receptor‐mediated apoptosis through the up‐regulation of Flip, but not apoptosis initiated by inhibition of the PI3K pathway.
In:
volume:31
In:
number:8
In:
year:2001
In:
pages:2421-2430
In:
extent:10
In:
European journal of immunology, Weinheim : Wiley-VCH, 1971-, 31, Heft 8 (2001), 2421-2430 (gesamt 10), 1521-4141
Language:
English
DOI:
10.1002/1521-4141(200108)31:8〈2421::AID-IMMU2421〉3.0.CO;2-W
URN:
urn:nbn:de:101:1-2023110506274787415630
URL:
https://doi.org/10.1002/1521-4141(200108)31:8〈2421::AID-IMMU2421〉3.0.CO;2-W
URL:
https://nbn-resolving.org/urn:nbn:de:101:1-2023110506274787415630
URL:
https://d-nb.info/1308667981/34
URL:
https://doi.org/10.1002/1521-4141(200108)31:8〈2421::AID-IMMU2421〉3.0.CO;2-W
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