Abstract:
:Among the tumor necrosis factor (TNF) family of cytokines, FasL and TNF-related apoptosis-inducing ligand (TRAIL) are known to induce cell death via caspase activation. Recently, other biological functions of these death ligands have been postulated in vitro and in vivo. It was previously shown that Fas ligation induces chemokine expression in human glioma cells. In this study, we investigated whether the TRAIL-DR5 system transduces signals similar to those induced by other TNF family ligands and receptors. To address this issue, two human glioma cell lines, CRT-MG and U87-MG, were used, and an agonistic antibody against DR5 (TRA-8) and human recombinant TRAIL were used to ligate DR5. We demonstrate that DR5 ligation by either TRAIL or TRA-8 induces two functional outcomes, apoptosis and expression of the chemokine interleukin-8 (IL-8); the nonspecific caspase inhibitor Boc-D-Fmk blocks both TRAIL-mediated cell death and IL-8 production; the caspase 3-specific inhibitor z-DEVD-Fmk suppresses TRAIL-mediated apoptosis but not IL-8 induction; caspase 1- and 8-specific inhibitors block both TRAIL-mediated cell death and IL-8 production; and DR5 ligation by TRAIL mediates AP-1 and NF-kappaB activation, which can be inhibited by caspase 1- and 8-specific inhibitors. These findings collectively indicate that DR5 ligation on human glioma cells leads to apoptosis and that the activation of AP-1 and NF-kappaB leads to the induction of IL-8 expression; these responses are dependent on caspase activation. Therefore, the TRAIL-DR5 system has a role not only as an inducer of apoptotic cell death but also as a transducer for proinflammatory and angiogenic signals in human brain tumors.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Choi C,Kutsch O,Park J,Zhou T,Seol DW,Benveniste ENdoi
10.1128/mcb.22.3.724-736.2002subject
Has Abstractpub_date
2002-02-01 00:00:00pages
724-36issue
3eissn
0270-7306issn
1098-5549journal_volume
22pub_type
杂志文章abstract::An accumulation in cells of unfolded proteins is believed to be the common signal triggering the induction of heat shock proteins (hsps). Accordingly, in Saccharomyces cerevisiae, inhibition of protein breakdown at 30 degrees C with the proteasome inhibitor MG132 caused a coordinate induction of many heat shock protei...
journal_title:Molecular and cellular biology
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doi:10.1128/mcb.18.1.30
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journal_title:Molecular and cellular biology
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1128/mcb.19.10.6815
更新日期:1999-10-01 00:00:00
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journal_title:Molecular and cellular biology
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pub_type: 杂志文章
doi:10.1128/mcb.11.9.4739
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更新日期:1983-04-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章,评审
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pub_type: 杂志文章
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更新日期:2001-01-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:1995-12-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.4.3136
更新日期:1999-04-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.10.4271
更新日期:1992-10-01 00:00:00