Project/Area Number |
17590631
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Gastroenterology
|
Research Institution | Jichi Medical University (2006) Mie University (2005) |
Principal Investigator |
MURATA Kazumoto Jichi Medical University, Center for Community Medicine, Associated professor, 医学部, 准教授 (40345971)
|
Co-Investigator(Kenkyū-buntansha) |
SHIRAKI Katsuya Mie University School of Medicine, The First Department of Internal Medicine, Lecturer, 医学部・附属病院, 講師 (90263003)
|
Project Period (FY) |
2005 – 2006
|
Project Status |
Completed (Fiscal Year 2006)
|
Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
|
Keywords | Proteasome / HBX protein / Vaccinia virus / Adeno virus / CTL assay / proteasome |
Research Abstract |
First, the expression of HBX protein was confirmed in adeno-HBX infected Renca cells (Balb/c mouse syngenic cell line), but not in adeno-HBX0 (HBX knockout) infected cells. Then, we examined MHC class I expression on the Renca cells infected with adeno-HBX or adeno-HBX0 (M.O.I.=0.5) 2 days after infection by flow cytometer. Its expression on the adeno-HBX infected Renca cells were significantly inhibited in comparison with that on the adeno-HBX0 infected Renca cells. Next, we tried to check the effect of HBX on cytotoxic lymphocyte (CTL) responses in vivo. We generated adeno-specific CTL clone by injection of adeno-LacZ to Balb/c mice intraperitoneally every 2 weeks, following ex vivo culture with fresh adeno-LacZ infected-dendritic cells for 7 days. A standard CTL assay was performed, using adeno-HBX infected Renca cells or adeno-HBX0 infected Renca cells as target cells. Chromium releasing was inhibited when we used adeno-HBX infected Renca cells as target cells, compared with adeno-HBX0 infected Renca cells. These results were quantitatively confirmed by intracellular cytokine (IFN-γ) staining. WE also examined these, using Vaccinia virus (vvHBX or vvHBX0). Both in vitro and in vivo study showed the same tendencies as using adeno-viruses. These pieces of evidences suggest that HBX inhibits antigen presentation through inhibition of proteasome. From these results, we speculate that HBX inhibits antoigen presentation through inhibition of proteasome, following immune escape.
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