HGM2002 Poster Abstracts: 8. Disease Mechanisms
POSTER NO: 421
Hepatitis B virus makes hepatocarcinoma cells resistant to TRAIL induced apoptosis
1Lihui Han, 1Wensheng Sun, 1Chunhong Ma, 2Youhai Chen
TNF-related apoptosis inducing ligand is a newly identified member of the TNF superfamily that has a powerful capability of inducing apoptosis. TRAIL could interact with five recepers(two death receptors, two decoy receptors and a soluble receptor) at the same time while other members of TNF superfamily could only bind to 1 or 2 receptors. The outstanding characteristic of TRAIL is that it could selectively induce drastic apoptosis of carcinoma cells and virus infected cells but spare the normal tissue cells. In our experiments we tried to find out what role HBV plays in the TRAIL induced apoptosis. Two human hepatocarcinoma cell lines, HepG2 and its HBV whole genome transgenic cell line named HepG2.2.15 were used in the experiments. HepG2 cells are sensitive to TRAIL induced apoptosis with the apoptosis rate of 51.6%, but HepG2.2.15 cells, which contain a whole HBV genome and could persistently secret virus particles, are rather resistant to TRAIL induced apoptosis with the apoptosis rate of 9.12%. It indicates that HBV play a pivotal role in the conversion of sensitivity of Hepatoma cells to TRAIL. The mRNA expression level of four receptors of TRAIL related to apoptosis are decreased to a more or less degree on HepG2.2.15 cells compared with HepG2 cells, but the expression of FLIP, a protein inhibiting apoptosis at the initial level of the caspase cascade, is drastically upregulated on HepG2.2.15 cells, which may explain the resistance of HBV infected cells to TRAIL induced apoptosis to a certain extent. Our results indicate that HBV could make cells resistant to TRAIL-induced apoptosis, this may be realized by the down-regulated expression of TRAIL and its receptors and up-regulated expression of FLIP. This offers us another explanation why HBV could escape the immune surveillance and persistently exist in the body. This may explain the pathogenesis of HBV related disease in a novel way.
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