Z Gastroenterol 2011; 49 - P5_20
DOI: 10.1055/s-0030-1269726

Effect of acute-phase cytokines on gene expression of DOR and other thyroid hormone receptors in rat liver and cultured liver cells

IA Malik 1, N Naila 2, F Moriconi 2, G Ramadori 2
  • 1Zentrum Innere Medizin Abt.Gastroenterologie u.Endokrinologie, Universitätsmedizin Göttingen Georg-August-Universität, Göttingen, Deutschland
  • 2Abt. Gastroenterologie und Endokrinologie, Uniklinikum Göttingen, Göttingen

Non-thyroidal-illness (NTI) is characterized by low tri-iodothyronine (T3) serum level under acute-phase-conditions. We studied hepatic gene expression of newly identified thyroid hormone receptor (TRs) cofactor DOR/TP53INP2 together with TRs in a model of aseptic abscesses induced by injecting intramuscular turpentine-oil (TO) in each hind limb. Liver cells (hepatocytes, macrophages and (myo)fibroblasts) were isolated from normal rat liver and treated with acute-phase cytokines. Hepatocytes were further treated with T3 in the presence or absence of IL-6.A fast (4–6h) decrease in serum-level of free thyroxine (FT4) and free tri-iodothyronine (FT3) was observed. By means of immunohistology, abundant DOR protein expression was detected in the nuclei of hepatocytes, ED-1 (mononuclear phagocytes), CK-19 (biliary cells) and SMA+-cells (mesenchymal-cells of portal tract). Reduction of DOR signals was observed with a minimum at 6–12h after acute- phase-reaction (APR). Immunohistology also showed a similar pattern of protein expression in TRα1 but without a significant change during APR. Transcripts specific for DOR, NCoR-1 and TRβ1 were down-regulated with a minimum at 6–12h, whereas TRα1 expression was slightly, and TRα2 expression was significantly up-regulated, with a maximum at 24h after APR was started. In cultured liver cells, the acute phase cytokines IL-1β and IL-6 down-regulated DOR and TRβ1 at mRNA levels. Moreover, gene expression of DOR and TRs-(TRα1. TRα2 and TRβ1) was up-regulated in hepatocytes by adding T3 to the culture medium and this up-regulation was almost completely blocked by the treatment of cells with IL-6. In conclusion, TRβ1, NCoR-1 and the recently identified DOR/TP53INP2 are abundantly expressed and down-regulated in liver cells during APR. Their down-regulation is due to the decreased serum level of thyroid hormones and most probably also to the direct action of the main acute-phase cytokines.