Project/Area Number |
07670573
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Gastroenterology
|
Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
TANAKA Yujiro Tokyo Medical and Dental University, Second Dept of Internal Medicine, Assistant, 医学部, 助手 (70236644)
|
Co-Investigator(Kenkyū-buntansha) |
ENOMOTO Nobuyuki Tokyo Medical and Dental University, Second Dept of Internal Medicine, Assistant, 医学部, 助手 (20251530)
|
Project Period (FY) |
1995 – 1996
|
Project Status |
Completed (Fiscal Year 1996)
|
Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥1,500,000 (Direct Cost: ¥1,500,000)
|
Keywords | HCV / cytotoxic T lymphocyte / apoptosis / necrosis / PCR |
Research Abstract |
In chronic hepatitis C,the involvement of cytotoxic T cells (CTLs) has been suspected mainly on the basis of histological findings of the liver. CTLs induce their target-cell death through perforin and/or Fas-ligand-Fas dependent pathways. The purpose of this study is to clarify the mechanism of CTL-mediated cytotoxicity in chronic hepatitis C by assessing the two pathways. The liver biopsy specimens were obtained from eight cases of chronic hepatitis C and, for comparison, four cases free of hepatitis C virus (HCV) after interferon treatment. Hepatic messenger RNAs of perforin, Fas-ligand, and CD8 were reverse transcribed, amplified inthe presence of their DNA competitors by polymerase chain reaction, and quantitated on an DNA Sequencer. Both hepatic mRNA levels of perforin and Fas-ligand, which were corrected by the level of CD8 mRNA,were elevated in chronic HCV infection, whereas they were nearly undetectable in the cases free of HCV.Among the cases of HCV infection, the ratio of Fas-ligand-mRNA/perforin-mRNA was significantly correlated with serum alanine aminotransferase levels (r=0.94). These results suggest the involvement of CTL-mediated cytotoxicity via both perforin and Fas-dependent pathways and the variable predominance of the dual pathways in chronic hepatitis C.
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