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

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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.