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Caspase-1 mediates Fas-induced apoptosis and
is up-regulated by interferon-gamma in human astrocytoma cells
Chulhee Choi, Eunjoo Jeong
and Etty N. Benveniste
Division of Molecular
Life Sciences and Center for Cell Signaling Research, Ewha Womans University,
Seoul, Korea (C.C., E.J.); Department of Cell Biology, University of Alabama at
Birmingham, Birmingham, AL, USA (C.C., E.N.B.). cchoi@ewha.ac.kr
Resistance to Fas-mediated apoptosis contributes to tumor evasion from the
host immune system and enables tumors to mediate alternative responses such as
inflammation and angiogenesis.
In this study, we investigated the molecular mechanisms of the resistance to
Fas-mediated apoptosis and sensitization to Fas-induced cell death by IFN-gamma
in human astrocytoma cells.
To address this, we investigated the expression of thirty-three genes related to
the Fas signal transduction pathways using RNase protection assay in five
different human astrocytoma cells.
Patterns of expression of these genes were similar between different cell lines
and did not correlate with sensitivity to Fas-mediated cell death.
Treatment with IFN-gamma increased the mRNA expression of caspases-1, -4 and -7
in addition to those of Fas and TRAIL in a time- and dose-dependent
manner.
Studies using specific caspase inhibitors showed that Fas-induced cell death was
mediated by caspases-1, -3 and 8 in the Fas-sensitive human astrocytoma cell
lines, CRT-J and U87-MG.
We further demonstrated that these caspases were proteolytically cleaved upon
Fas ligation in these cells.
Interestingly, caspase-1 protein expression but not that of caspase-3 nor -8 was
up-regulated by IFN-gamma only in Fas-sensitive CRT-J cells but not in
Fas-resistant U373-MG cells.
These results collectively suggest that caspase-1, along with caspases-3 and -8,
mediate Fas-induced cell death in human astrocytoma cells, and
post-transcriptional regulation of caspase-1 may determine the responsiveness to
IFN-gamma-induced sensitization to Fas-mediated apoptosis.
PMID: 15072464 [PubMed - indexed for MEDLINE]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15072464
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