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and interleukin 6 decrease nuclear thyroid hormone receptor capacity in a liver cell line
Wolf M, Hansen N, Greten H. Interleukin 1β, tumor necrosis factor-
and interleukin 6 decrease nuclear thyroid hormone receptor capacity in a liver cell line. Eur J Endocrinol 1994;131:307–12. ISSN 0804–4643
Many of the acute inflammatory responses in critical illness are mediated by tumor necrosis factor-
(TNF-
), interleukin 1/3 (IL-1β) 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-
, IL-1β 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 1β 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 µg/l IL-1β respectively. Interleukin 6 and TNF-
significantly reduced receptor capacity only at concentrations of 10 µg/l or higher and the magnitude of the reduction was lower than with IL-1β. 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 µg/l IL-6 or TNF-
. respectively. TR affinity was not altered significantly after stimulation with any of the cytokines. In conclusion, we present evidence that the capacity of hepatic nuclear TRs is regulated by IL-1β. IL-6 and TNF-
. As cellular reaction to thyroid hormone stimulation depends on the number of nuclear TRs, this mechanism may serve to restrict catabolic effects of thyroid hormones during acute illness.
M Wolf, Medizinische Kern- und Poliklinik, Universitäts-Krankenhaus Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany
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