Interleukin 1 beta, tumor necrosis factor-alpha and interleukin 6 decrease nuclear thyroid hormone receptor capacity in a liver cell line.
Many of the acute inflammatory responses in critical illness are mediated by tumor necrosis factor-alpha (TNF-alpha), interleukin 1 beta (IL-1 beta) and interleukin 6 (IL-6). Furthermore, these cytokines are involved in mediating the characteristic changes of thyroid function during acute disease known as non-thyroidal illness. In the present studies we investigated in vitro whether TNF-alpha, IL-1 beta and IL-6 modify nuclear thyroid hormone receptor (TR) capacity and/or affinity. Regulation of TR synthesis was studied in the human hepatoma cell line Hep-G2. Subconfluent cells were incubated with recombinant cytokines in serum-free medium. Nuclear extracts were prepared by high-salt extraction of cell nuclei. Binding assays were performed with [125I]-triiodothyronine; bound and free hormone were separated by filtration. Interleukin 1 beta decreased TR capacity in a dose-dependent manner. Compared with unstimulated cells, the TR capacity was reduced to 87.9 +/- 3.9% (p < 0.05), 80.1 +/- 3.9% (p < 0.01) and 72.1 +/- 5.1% (p < 0.01) after incubation with 0.1, 1.0 and 100 micrograms/l IL-1 beta, respectively. Interleukin 6 and TNF-alpha significantly reduced receptor capacity only at concentrations of 10 micrograms/l or higher and the magnitude of the reduction was lower than with IL-1 beta. The TR capacity was reduced to 81.2 +/- 2.3% (p < 0.01) and 83.2 +/- 6.6% (p < 0.05) after stimulation with 10 micrograms/l IL-6 or TNF-alpha, respectively. TR affinity was not altered significantly after stimulation with any of the cytokines.(ABSTRACT TRUNCATED AT 250 WORDS)
Wolf
M
M
Medizinische Kernklinik und Poliklinik, Universitäts-Krankenhaus Eppendorf, Hamburg, Germany.
Hansen
N
N
Greten
H
H
D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D011988:Receptors, Thyroid Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D015850:Interleukin-6; D011988:Receptors, Thyroid Hormone; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha