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Role of thymocyte differentiation in the progression of primary biliary cirrhosis

Research Project

Project/Area Number 17590655
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionKochi University

Principal Investigator

ONICHI Saburo  Kochi University, Kochi Medical School, Gastroenterology and Hepatology, professor, 医学部, 教授 (60136380)

Co-Investigator(Kenkyū-buntansha) SAIBARA Toshiji  Kochi University, Kochi Medical School, Gastroenterology and Hepatology, adjunct professor, 医学部, 助教授 (60145125)
AKISAWA Naoaki  Kochi University, Kochi Medical School, Gastroenterology and Hepatology, assistant professor, 医学部, 助手 (00322280)
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: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥2,400,000 (Direct Cost: ¥2,400,000)
KeywordsPBC / cholasngitis / autoimmunity / thymocyte / differentiation / estrogen / epithelial cell / 非アルコール性脂肪肝炎(NASH) / NASH動物モデル / 肝線維化 / インスリン抵抗性 / 肥満
Research Abstract

Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized with nonsuprative destructive cholangitis that results in liver cirrhosis and liver failure. This disease is rather frequent in female older than 40s. In our previous study, menopausal changes were suggested as one of the most important trigger for the development of autoimmune responses to a variety of organs. Abrupt decrease in plasma estrogen levels may affect so much on the progression of this disease, we believe. Thus in this study, we inquired the development of thymocytes in estrogen deficient mice and proved impaired development of CD4+CD8+CD25+ thymocytes. Impaired development of thymocytes with TCR β in high intensity could be involved in the development of autoimmunity as these cells are potent enough to suppress B cell proliferation.
In the two-year project, we showed B cell are more prominently proliferating in bone marrow and in the liver in estrogen deficient mice and exogeneous estrogens are able to attenuate B cell proliferation significantly. Therefore, we transferred allogeneic spleen cells to estrogen deficient mice and induced chronic cholangitis for assessing destructive changes of biliary epithelium and inflammatory changes. Destructive changes and inflammatory cell infiltration were apparently more severe in estrogen-deficient recipients than in wild type recipients. Exogenously administered estrogens were very potent to attenuate damages of biliary epithelium. From these observations we deduce that destruction of biliary epithelium via immunological mechanism could be deteriorated profoundly by estrogen deficiency in postmenopausal stage.

Report

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

    (38 results)

All 2006 2005

All Journal Article (24 results) Book (14 results)

  • [Journal Article] Interferon-beta plus ribavirin for patients with hepatitis C virus genotype 1 : a randomized pilot study.2006

    • Author(s)
      M.Enomoto, et al.
    • Journal Title

      Gut 55

      Pages: 139-140

    • 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] In vivo imaging of hepatic fatty acid metabolism in patients with non-alcoholic steatohepatitis using semiquantitative I-labeled branched-chain fatty acid analog.2006

    • Author(s)
      Onishi S, et al.
    • Journal Title

      J Gastroenterol Hepatol. 21 Suppl 3

    • 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] In vivo imaging of hepatic fatty acid metabolism in patients with non-alcoholic steatohepatitis using semiquantitative I-labeled branched-chain fatty acid analog.2006

    • Author(s)
      Onishi S, et al.
    • Journal Title

      J Gastroenterol Hepatol. 21(Suppl 3)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] CYP17 polymorphism as a risk factor of tamoxifen-induced hepatic steatosis in breast cancer patients2005

    • Author(s)
      T.Ohnishi, et al.
    • Journal Title

      Oncol Rep 13

      Pages: 465-489

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Similar anti-mitochondrial antibody reactivity profiles in familial primary biliary cirrhosis.2005

    • Author(s)
      Y.Hayase, et al.
    • Journal Title

      Hepatol Res 33

      Pages: 33-38

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] In vivo imaging of hepatic fatty acid metabolism in patients with nonalcoholic steatohepatitis using semiquantative 123I-BMIPP liver scan.2005

    • Author(s)
      Fukumoto M, et al.
    • Journal Title

      Hepatol Res 33

      Pages: 105-109

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] CYP17 polymorphism and tamoxifen-induced hepatic steatosis2005

    • Author(s)
      T.Ohnishi, et al.
    • Journal Title

      Hepatol Res 33

      Pages: 178-180

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Similar anti-mitochondrial antibody reactivity profiles in familial primary biliary cirrhosis.2005

    • Author(s)
      Y.Hayase
    • Journal Title

      Hepatology Research 33

    • Related Report
      2005 Annual Research Report
  • [Journal Article] CYP17 polymorphism as a risk factor of tamoxifen-induced hepatic steatosis in breast cancer patients.2005

    • Author(s)
      Onishi T
    • Journal Title

      Oncol Rep 13

      Pages: 465-489

    • Related Report
      2005 Annual Research Report
  • [Journal Article] In vivo imaging of hepatic fatty acid metabolism in patients with nonalcoholic steatohepatitis using semiquantative 123I-BMIPP liver scan.2005

    • Author(s)
      Fukumoto M
    • Journal Title

      Hepatol Res 33

      Pages: 105-109

    • Related Report
      2005 Annual Research Report
  • [Journal Article] インスリン抵抗性とNASH2005

    • Author(s)
      西原利治
    • Journal Title

      日本内科学会雑誌 95

      Pages: 46-50

    • Related Report
      2005 Annual Research Report
  • [Journal Article] NASHにおけるmicrosomal triglyceride transfer proteinとManganese superoxide dismutaseの遺伝子多型の検討2005

    • Author(s)
      並川智香子
    • Journal Title

      医学と薬学 53

      Pages: 93-95

    • Related Report
      2005 Annual Research Report
  • [Journal Article] NASHの治療2005

    • Author(s)
      西原利治
    • Journal Title

      消化器内視鏡 17

      Pages: 83-88

    • Related Report
      2005 Annual Research Report
  • [Journal Article] NASHの遺伝的背景2005

    • Author(s)
      西原利治
    • Journal Title

      消化器科 40

      Pages: 66-71

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 脂肪肝:NASH2005

    • Author(s)
      西原利治
    • Journal Title

      Medicina 42

      Pages: 234-235

    • Related Report
      2005 Annual Research Report
  • [Journal Article] NASHの臨床像と治療2005

    • Author(s)
      西原利治
    • Journal Title

      日本臨床 54

      Pages: 500-502

    • Related Report
      2005 Annual Research Report
  • [Journal Article] NASH(非アルコール性脂肪肝炎)の現況2005

    • Author(s)
      西原利治
    • Journal Title

      日本薬剤師会雑誌 57

      Pages: 605-607

    • Related Report
      2005 Annual Research Report
  • [Journal Article] NASHの臨床像と治療2005

    • Author(s)
      西原利治
    • Journal Title

      総合臨床 54

      Pages: 500-502

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 非アルコール性脂肪肝炎と糖尿病2005

    • Author(s)
      西原利治
    • Journal Title

      糖尿病 48

      Pages: 243-245

    • NAID

      10015650475

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 非アルコール性脂肪肝炎(NASH)の実態と課題2005

    • Author(s)
      西原利治
    • Journal Title

      日本医師会雑誌 134

      Pages: 633-635

    • Related Report
      2005 Annual Research Report
  • [Journal Article] NASHの病理組織像2005

    • Author(s)
      円山英昭
    • Journal Title

      Progress in Medicine 25

      Pages: 1623-1628

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 特集:NAFLDの成因 序文2005

    • Author(s)
      西原利治
    • Journal Title

      細胞 37

      Pages: 336-336

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 脂肪肝とNASHにおける年齢・性差2005

    • Author(s)
      西原利治
    • Journal Title

      肝胆膵 51

      Pages: 227-233

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 薬物起因性NASH2005

    • Author(s)
      西原利治
    • Journal Title

      医学のあゆみ 214

      Pages: 888-892

    • Related Report
      2005 Annual Research Report
  • [Book] NAFLDのすべて2006

    • Author(s)
      西原利治, 大西三朗
    • Publisher
      医歯薬出版
    • 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
  • [Book] 「消化器疾患」II肝胆膵2006

    • Author(s)
      西原利治, 大西三朗
    • Total Pages
      726
    • Publisher
      医歯薬出版
    • 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
  • [Book] 消化器疾患の診断基準、病型分類、重症度の用い方(非アルコール性脂肪肝炎の診断基準)2006

    • Author(s)
      西原利治, 大西三朗
    • Total Pages
      369
    • Publisher
      日本メディカルセンター
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] 図解消化器内科学テキスト(脂肪肝、非アルコール性脂肪肝炎)2006

    • Author(s)
      西原利治, 小野正文, 大西三朗
    • Total Pages
      445
    • Publisher
      中外医学社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] 消化器疾患ガイドライン(非知レコール性脂肪性肝疾患)2006

    • Author(s)
      西原利治, 大西三朗
    • Total Pages
      247
    • Publisher
      総合医学社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] 「消化器疾患の診断基準、病型分類、重症度の用い方」非アルコール性脂肪肝炎の診断基準2006

    • Author(s)
      西原利治, 大西三朗
    • Total Pages
      369
    • Publisher
      日本メディカルセンター
    • Related Report
      2006 Annual Research Report
  • [Book] 「図解消化器内科学テキスト」脂肪肝、非アルコール性脂肪肝炎2006

    • Author(s)
      西原利治, 小野正文, 大西三朗
    • Total Pages
      445
    • Publisher
      中外医学社
    • Related Report
      2006 Annual Research Report
  • [Book] 「消化器疾患ガイドライン」非アルコール性脂肪性肝疾患2006

    • Author(s)
      西原利治, 大西三朗
    • Total Pages
      247
    • Publisher
      総合医学社
    • Related Report
      2006 Annual Research Report
  • [Book] 非アルコール性脂肪性肝炎(NASH)2005

    • Author(s)
      西原利治
    • Total Pages
      58
    • Publisher
      メディカルレビュー社
    • Related Report
      2005 Annual Research Report
  • [Book] NASH and Nutritional Therapy2005

    • Author(s)
      T.Saibara
    • Total Pages
      117
    • Publisher
      Springer-Verlag Tokyo
    • Related Report
      2005 Annual Research Report
  • [Book] 消化器疾患最新の治療2005-20062005

    • Author(s)
      西原利治
    • Total Pages
      476
    • Publisher
      南江堂
    • Related Report
      2005 Annual Research Report
  • [Book] 肝疾患と免疫2005

    • Author(s)
      西原利治
    • Total Pages
      179
    • Publisher
      医薬ジャーナル社
    • Related Report
      2005 Annual Research Report
  • [Book] 消化器学2005

    • Author(s)
      西原利治
    • Total Pages
      649
    • Publisher
      メジカルビュー社
    • Related Report
      2005 Annual Research Report
  • [Book] 酸化ストレスと肝疾患2005

    • Author(s)
      西原利治
    • Total Pages
      138
    • Publisher
      アークメディア社
    • Related Report
      2005 Annual Research Report

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

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