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The mechanism of chronicity of hepatitis B (inhibition of antigen presentation by HBX protein)

Research Project

Project/Area Number 17590631
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionJichi 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)
KeywordsProteasome / 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.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (31 results)

All 2007 2006 2005 Other

All Journal Article (31 results)

  • [Journal Article] 脾摘術にて肝不全を離脱し得た非代償性肝硬変の2例2007

    • Author(s)
      伊藤圭一
    • Journal Title

      肝臟 47

      Pages: 30-37

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A novel mechanism for drug-induced liver failure : inhibition of histone acetylation by hydralazine derivatives.2007

    • Author(s)
      Murata K
    • Journal Title

      J Hepatol 46

      Pages: 322-329

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Gastric metastases from anaplastic pancreatic cancer2007

    • Author(s)
      Murata K
    • Journal Title

      Clin Gastroenterol Hepatol 5

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Isoleucine, an essential amino acid, prevents liver metastases of colon cancer by antiangiogenesis.2007

    • Author(s)
      Murata K
    • Journal Title

      Cancer Res 67(7)

      Pages: 3263-3268

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Gastric metastases from anaplastic pancreatic cancer.2007

    • Author(s)
      Murata k
    • Journal Title

      Clin Gastroenterol Hepatol 5

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Isoleucine, an essential aminoacid, prevents liver metastases of colon cancer by antiangiogenesis.2007

    • Author(s)
      Murata K
    • Journal Title

      Cancer Res 67

      Pages: 3263-3268

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 脾摘術にて肝不全を離脱し得た非代償性肝硬変の2例2007

    • Author(s)
      伊藤圭一
    • Journal Title

      肝臓 47

      Pages: 30-37

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A novel mechanism for drug-inducedl liver failure : inhibition of histone acetylation by hydralazine derivatives.2007

    • Author(s)
      Murata K
    • Journal Title

      J Hepatol 46

      Pages: 322-329

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Identification of novel hepatitis C virus-specific cytotoxic T lymphocyte epitope in NS3 region.2006

    • Author(s)
      Ito K
    • Journal Title

      Hepatol Res 36

      Pages: 294-300

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Splenectomy rescues patients of liver cirrhosis with hypersplenism from liver failure2006

    • Author(s)
      Ito K
    • Journal Title

      Acta Hepatologica Japonica 47

      Pages: 30-37

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Noninvasive estimation of liver fibrosis and response to interferon therapy by a serum fibrogenesis marker, YKL-40, in patients with HCV-associated liver disease.2005

    • Author(s)
      Saitou Y
    • Journal Title

      World J Gastroenterol 11

      Pages: 476-481

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cholangiocarcinoma with chylous ascites.2005

    • Author(s)
      Yamamoto N
    • Journal Title

      J Gastroenterol Hepatol 19

      Pages: 1417-1417

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Functional expression of TWEAK in human colonic adenocarcinoma cells.2005

    • Author(s)
      Kawakita T
    • Journal Title

      Int J Oncol 26

      Pages: 87-93

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Macrocytic anemia during low-dose cisplatin and 5-fluorouracil through implanted infusion port for unresectable hepatobilliary malignancies.2005

    • Author(s)
      Yamamoto N
    • Journal Title

      Anticancer Res 25

      Pages: 1243-1246

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Sclerosing encapsulating peritonitis.2005

    • Author(s)
      Yamamoto N
    • Journal Title

      J Gastroenterol Hepatol 20

      Pages: 952-952

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cytomegalovirus infection with various clinical symptoms.2005

    • Author(s)
      Matsuda A
    • Journal Title

      Nippon Naika Kakkai Zasshi 94

      Pages: 346-348

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Up-regulation of IL-18 by interferon alpha/ribavirin combination therapy induces an anti-viral effect in patients with chronic hepatitis C.2005

    • Author(s)
      Murata K
    • Journal Title

      Hepato=Gastroenterol 11

      Pages: 547-551

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cardiac metastases of gallbladder carcinoma.2005

    • Author(s)
      Inoue T
    • Journal Title

      World J Gastroenterol 11

      Pages: 2048-2049

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Expression of TNF-related apoptosis-inducing ligand in human hepatocellular carcinoma.2005

    • Author(s)
      Shiraki K
    • Journal Title

      Int J Oncol 26

      Pages: 1273-1281

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Tumor thrombi in esophageal varices.2005

    • Author(s)
      Sugimoto K
    • Journal Title

      J Gastroenterol Hepatol 20

      Pages: 651-651

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Functional expression of a proliferation-related ligand in hepatocellular carcinoma and its implication for neovascularization.2005

    • Author(s)
      Okano H
    • Journal Title

      World J Gastroenterol 11

      Pages: 4650-4654

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A case report of primary biliary cirrhosis after aortoiliac reconstruction surgery using Y-graft.2005

    • Author(s)
      Inoue T
    • Journal Title

      World J Gastroenterol 11

      Pages: 6219-6220

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Relative predictive factors for hepatocellular carcinoma after HBeAg seroconversion in HBV infection.2005

    • Author(s)
      Murata K
    • Journal Title

      World J Gastroenterol 11

      Pages: 6848-6852

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Remission of bronchial asthma after viral clearance in chronic hepatitis C.2005

    • Author(s)
      Yamamoto N
    • Journal Title

      World J Gastroenterol 11

      Pages: 7545-7545

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cholangiocarcinoma with chylous ascites2005

    • Author(s)
      Yamamoto N, Shiraki K, Yamanaka Y, Sugimoto K, Murata K, Nakano T
    • Journal Title

      J Gastroenterol Hepatol 19

      Pages: 1417-1417

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Macrocytic anemia during low-dose cisplatin and 5-FU through implanted infusion port for unresectable hepatobiliary malignancies2005

    • Author(s)
      Yamamoto N, Murata K, Fuke H, et al.
    • Journal Title

      Anticancer Res 25

      Pages: 1243-1246

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Sclerosing encapsulating peritonitis2005

    • Author(s)
      Yamamoto N, Ishikawa E, Murata K
    • Journal Title

      J Gastroenterol Hepatol 20

      Pages: 953-953

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Cytomegalovirus infection with various clinical symptoms2005

    • Author(s)
      Masuda A, Yamamoto N, Murata K, Shiraki K, Isaka N, Nakano T
    • Journal Title

      Nippon Naika Gakkai Zasshi 94

      Pages: 346-348

    • NAID

      10015501078

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Up-regulation of IL-18 by IFN alpha/ribavirin combination therapy induces an anti-viral effect in patients with chronic hepatitis C2005

    • Author(s)
      Murata K, Yamamoto N, Kawakita T, et al.
    • Journal Title

      Hepato-Gastroenterology 52

      Pages: 547-551

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Relative predictive factors for hepatocellular carcinoma after HBeAg seroconversion in HBV infection2005

    • Author(s)
      Murata K, Sugimoto K, Shiraki K, Nakano T
    • Journal Title

      World J Gastroenterol 43

      Pages: 6848-6852

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Isoleucine, anessential amino acid, prevents liver metastases of colon cancer by antiangiogenesis.

    • Author(s)
      Murata K
    • Journal Title

      Cancer Res (In press)

    • Related Report
      2006 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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