[The influence of HBV infection on TRAIL-induced apoptosis and its mechanism].
OBJECTIVE
The aim of this study was to investigate whether Hepatitis B virus will influence TRAIL (TNF-related apoptosis inducing ligand) induced apoptosis of the target cells.


METHODS
Two human hepatocellular carcinoma cell lines, HepG2 and its HBV whole genome transgenic cell line named HepG2.2.15 were observed in the experiments. The apoptosis rates of these two cell lines to TRAIL were examined by flow cytometry. The expression of the membrane-bound TRAIL and the secretory soluble TRAIL in the supernatant were assessed by flow cytometry and enzyme-linked immunosorbent assay, respectively. The expression of the mRNA of TRAIL receptors and FLIP were assessed by semi-quantitive PCR.


RESULTS
In contrast to HepG2 cell line, the apoptosis rate of HepG2.2.15 cell line to TRAIL was significantly low (9.12% vs 51.6%, P < 0.01). The mRNA expression of four TRAIL receptors related to apoptosis were 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, was drastically upregulated on HepG2.2.15 cells (P < 0.01). There's no significant difference in the secretory TRAIL expression between these two cell lines.


CONCLUSIONS
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 offer us another explanation why HBV could escape the immune surveillance and persistently exist in the body, which may explain the pathogenesis of HBV related disease in a novel way.
Han
Lihui
L
Department of Microbiology and Immunology, Shandong Medical University, Jinan 250012, China.
Sun
Wensheng
W
Ma
Chunhong
C
Zhang
Lining
L
Cao
Yinglin
Y
Song
Jing
J
Chen
Youhai
Y
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000378:metabolism; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000821:virology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D051017:Apoptosis Regulatory Proteins; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha