| Project/Area Number |
12671078
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | Nagoya University |
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Principal Investigator |
NAGAYA Takashi Nagoya Univ, Res Inst. Emviron. Med, Research Associate, 環境医学研究所, 助手 (80262913)
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| 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)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| 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)
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| Keywords | Thyroid 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.
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