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Functional crosstalk between transcription factor NF-kB and thyroid hormone receptor

Research Project

Project/Area Number 12671078
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionNagoya University

Principal Investigator

NAGAYA Takashi  Nagoya Univ, Res Inst. Emviron. Med, Research Associate, 環境医学研究所, 助手 (80262913)

Co-Investigator(Kenkyū-buntansha) KAMBE Fukushi  Nagoya Univ, Res Inst. Emviron. Med, Associate Professor, 環境医学研究所, 助教授 (00211871)
SEO Hisao  Nagoya Univ, Res Inst. Emviron. Med, Professor, 環境医学研究所, 教授 (40135380)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥2,700,000 (Direct Cost: ¥2,700,000)
KeywordsThyroid hormone receptor / NF-kB / euthyroid sick syndrome / Cytokine / Thyroid hormone / NF-кB / 甲状腺ホルモン受容体 / TNFα / 悪液質 / 組換えアデノウイルス
Research Abstract

To elucidate the effect of TNFa-induced NF-kB on thyroid hormone action, we focused the studies on liver that is one of the target organs of thyroid hormone.
Using human hepatoblastoma-drived HepG2 cells, we demonstrated that an increase of 5'deiodinase(5'DI) mRNA expression by T3 was deteriorated in the presence of TNFa in Northern blot analysis. In transfection assays using 5'-DI promoter luciferase reporter gene, the induction of 5'-DI Luc activity by T3 was reduced with the treatment of TNFa, in concordance with the results of Northern blot analysis. To study whether this inhibitory effect of TNFa is due to activated NF-kB, we used dominant negative NF-kB(p65 DN) as a tool. The inhibition of T3-dependent increase of 5'-DI mRNA or Luc activity by TNFa was prevented by introducing p65 DN, suggesting that the inhibitory effect was mediated through NF-kB. In euthyroid wick syndrome observed in severe conditions of sepsis, etc., elevated circulating TNFa and decreased hepatic 5' DI activity by TNFa-induced NF-kB would be involved in the pathogenesis of euthyroid sick syndrome.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Kikumori T, 他: "Thyrotropin modifies activation of nuclear factor-κB by tumor necrosis factor α in rat thyroid cell line"Biochem. J.. 354. 573-579 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nagaya T, 他: "A Potential role of activated NF-κB in the pathogenesis of euthyroid sick syndrome"J. Clin. Invest.. 106. 393-402 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sarkar D, 他: "Culture in vector-averaged gravity under clinostat rotation results in apoptosis of osteoblastic ROS 17/2.8 cells"J Bone Miner. Res.. 15. 489-498 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 長屋敬, 他: "NF-κBと核内受容体のクロストーク"内分泌・糖尿病科. 10. 348-356 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 長屋敬, 他: "レチノイドX受容体(RXR)の蛋白分解による甲状腺ホルモン作用の修飾"ホルモンと臨床. 48. 31-39 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kikumori T, Kambe F, Nagaya T, Funahashi H, Seo H.: "Thyrotropin modifies activation of nuclear factor-kB by tumor necrosis factor a in rat thyroid cell line"Biochem. J.. 34. 573-579 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nagaya T, Fujieda M, Ohtsuka G, J-P. Young, Okamoto T, Seo H.: "A potential role of activated NF-kB in the pathogenesis of euthyroid sick syndrome"J. Clin. Invest. 106. 393-402 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sarkar D, Nagaya T, Koga K, Nomura Y, Gruener R, Seo H: "Culture in vector-averaged gravity under clinostat rotation results in apoptosis of osteoblastic ROS17/2.8 cells"J. Bone Miner. Res.,. 15. 489-498 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kikumori T, 他: "Thyrotropin modifies activation of nuclear factor-кB by tumor necrosis factor α in rat thyroid cell line"Biochem. J.. 354. 573-579 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nagaya T, 他: "A Potential role of activated NF-кB in the pathogenesis of euthyroid sick syndrome"J. Clin. Invest.. 106. 393-402 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sarkar D, 他: "Culture in vector-averaged gravity under clinostat rotation results in apoptosis of osteoblastic ROS 17/2.8 cells"J. Bone Miner. Res.. 15. 489-498 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] 長屋 敬, 他: "NF-кBと核内受容体のクロストーク"内分泌・糖尿病科. 10. 348-356 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] 長屋 敬, 他: "レチノイドX受容体(RXR)の蛋白分解による甲状腺ホルモン作用の修飾"ホルモンと臨床. 48. 31-39 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nagaya T 他: "A potential role of activated NF-κB in the pathogenesis of euthyroid sick syndrome."J.Clin.Invest.. 106. 393-402 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sarkar D 他: "Culture in vector-averaged gravity under clinostat rotation results in apoptosis of osteoblastic ROS 17/2.8 cells."J.Bone Miner.Res.. 15. 489-498 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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