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IFN-γinduces cell death in human hepatoma cells through a trail/death receptor-mediated apoptotic pathway

Title
IFN-γinduces cell death in human hepatoma cells through a trail/death receptor-mediated apoptotic pathway
Authors
Eui-Cheol Shin;Ju Mi Ahn;Jeon Han Park;Se Jong Kim;Hoguen Kim;Young Soo Ahn;Youjeong Choi;Chul Hoon Kim
Issue Date
2001
Journal Title
International Journal of Cancer
ISSN
0020-7136
Citation
International Journal of Cancer, Vol.93(2) : 262~268, 2001
Abstract
We demonstrated the induction of cell death in a hepatoma cell line by IFN-gamma and its possible mechanism. Among the 2 hepatitis B virus (HBV)-associated hepatoma cell lines, SNU-354 and SNU-368, IFN-gamma induced cell death and increased caspase-3 activity in SNU-368 but not in SNU-354. IFN-gamma induced several changes in the mRNA expression level of apoptosis-regulating genes, e.g., increased expression of Fas, caspase-1 and TNF-related apoptosis-inducing ligand (TRAIL). In particular, IFN-gamma potently increased the mRNA expression of TRAIL in both cell lines. However, it did not change the mRNA expression level of death-mediating TRAIL receptors, e.g., DR4 and DR5, which were constitutively expressed in both cell lines. In contrast, the decoy receptor DcR1 was expressed in SNU-354 but not in SNU-368, and its expression level in SNU-354 was increased by IFN-gamma. Another decoy receptor, DcR2, was constitutively expressed in both cell lines; however, its expression level in SNU-368 was decreased by IFN-gamma. In addition, exogenous recombinant TRAIL reduced viability in SNU-368, but not in SNU-354, cells. From these findings, we speculated that TRAIL up-regulation and the subsequent TRAIL-mediated apoptosis serve as a mechanism of IFN-gamma-induced cell death in SNU-368. To confirm this hypothesis, we demonstrated that soluble DR4-Fc fusion protein, a TRAIL pathway inhibitor, inhibited IFN-gamma-induced cell death in SNU-368. Our results demonstrated that IFN-gamma acts as an inducer of cell death through TRAIL-mediated apoptosis.
URI
http://onlinelibrary.wiley.com/doi/10.1002/ijc.1310/abstract

http://ir.ymlib.yonsei.ac.kr/handle/22282913/142092
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Pharmacology
1. 연구논문 > 1. College of Medicine > Dept. of Pathology
1. 연구논문 > 1. College of Medicine > Dept. of Microbiology
Yonsei Authors
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