Chronic hepatitis B serum promotes apoptotic damage in human renal tubular cells.
OBJECTIVE
To investigate the effect of the serum of patients with chronic hepatitis B (CHB) on apoptosis of renal tubular epithelial cells in vitro and to study the role of hepatitis B virus (HBV) and transforming growth factor-beta (1) (TGF-beta (1)) in the pathogenesis of hepatitis B virus associated glomerulonephritis (HBV-GN).


METHODS
The levels of serum TGF-beta(1) were measured by specific enzyme linked immunosorbent assay (ELISA) and HBV DNA was tested by polymerase chain reaction (PCR) in 44 patients with CHB ,and 20 healthy persons as the control. The normal human kidney proximal tubular cell (HK-2) was cultured together with the sera of healthy persons, CHB patients with HBV-DNA negative (20 cases) and HBV-DNA positive (24 cases) for up to 72 h. Apoptosis and Fas expression of the HK-2 were detected by flow cytometer.


RESULTS
The apoptosis rate and Fas expression of HK-2 cells were significantly higher in HBV DNA positive serum group 19.01%+/-5.85% and 17.58%+/-8.35%, HBV DNA negative serum group 8.12%+/-2.80% and 6.96%+/-2.76% than those in control group 4.25%+/-0.65% and 2.33%+/-1.09%, respectively (P<0.01). The apoptosis rate and Fas expression of HK-2 in HBV DNA positive serum group was significantly higher than those in HBV DNA negative serum (P<0.01). Apoptosis rate of HK-2 cells in HBV DNA positive serum group was positively correlated with the level of HBV-DNA (r = 0.657). The level of serum TGF-beta (1) in CHB group was 163.05+/-91.35 microg/L, significantly higher as compared with 81.40+/-40.75 microg/L in the control group (P<0.01).


CONCLUSIONS
The serum of patients with chronic hepatitis B promotes apoptotic damage in human renal tubular cells by triggering a pathway of Fas up-regulation. HBV and TGF-beta (1) may play important roles in the mechanism of hepatitis B virus associated glomerulonephritis.
Deng
Cun-Liang
CL
Department of Infectious Diseases, Affiliated Hospital of Luzhou Medical College, Luzhou 646000, Sichuan Province, China. dengcunl64@vip.sina.com
Song
Xin-Wen
XW
Liang
Hai-Jun
HJ
Feng
Chen
C
Sheng
Yun-Jian
YJ
Wang
Ming-Yong
MY
D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D017077:Culture Media, Conditioned; D004279:DNA, Viral / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005921:Glomerulonephritis / Q000821:virology*; D006515:Hepatitis B virus / Q000235:genetics / Q000472:pathogenicity*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000503:physiopathology*; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology*; D016133:Polymerase Chain Reaction; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000097:blood / Q000502:physiology*; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation; D019014:fas Receptor
D017077:Culture Media, Conditioned; D004279:DNA, Viral; C491901:FAS protein, human; D018124:Receptors, Tumor Necrosis Factor; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019014:fas Receptor