AI Article Synopsis
- IFNgamma and IFNalpha are important molecules produced by activated CTLs and NK cells that inhibit the expression of the decoy receptor TRAILR4 on cell surfaces.
- The down-regulation of TRAILR4 is linked to proteasome activity, as evidenced by the effectiveness of protease inhibitor cocktails and MG132.
- Reducing TRAILR4 expression through siRNA enhances sensitivity to TRAIL-induced apoptosis, suggesting that interferons promote cell death not just by increasing TRAIL levels but also by decreasing TRAILR4, which normally blocks apoptosis.
Article Abstract
IFNgamma and its transcriptional target tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) are two major effector molecules of activated CTLs and NK cells. Here, we show that IFNgamma as well as the type I interferon IFNalpha strongly inhibit cell surface expression of the decoy receptor TRAILR4 while having only a moderate inhibitory or even an inducing effect on TRAILR2 and CD95. Interferon-induced inhibition of TRAILR4 expression was blocked by a protease inhibitor cocktail and also by MG132, suggesting that down-regulation of TRAILR4 involves the proteasome. Inhibition of TRAILR4 expression by siRNA sensitized for TRAIL-, but not CD95L-induced apoptosis. Thus, the apoptosis-inducing action of interferons may not only rely on the well-established induction of TRAIL in effector cells but also on concomitant down-regulation of its antagonizing decoy receptor TRAILR4 in target cells.
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| http://dx.doi.org/10.1016/j.bbrc.2005.09.039 | DOI Listing |
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