R Ebert-Dümig

Publications (3)10.21 Total impact

• Article: [Expression of selenoproteins in monocytes and macrophages--implications for the immune system].

  R Ebert-Dümig, J Seufert, D Schneider, J Köhrle, N Schütze, F Jakob
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  ABSTRACT: Monocytes differentiate from myeloid precursors towards the macrophage state of differentiation under the influence of 1,25-dihydroxy vitamins D3 (1,25 [OH]2 vitamin D3) and other factors and this is further propagated by colony stimulating factors (MCSF and GMCSF). Macrophage activation and phagocytosis of foreign particles are regularly accompanied by a so called "respiratory burst", an increase in the production of reactive oxygen species (ROS), exerted by the enzyme complex NADPH oxidase. A number of antioxidant enzymes is expressed at the same time to protect the cells from the cytotoxic effects of ROS directed against engulfed microorganisms. The selenium-dependent glutathione peroxidases and thioredoxin reductases are important examples. The cytosolic GPx isoenzyme (cGPx) and thioredoxin reductase alpha (TrxR alpha) are upregulated during the process of differentiation and under the influence of 1.25 (OH)2 vitamin D3. GPx isoenzymes neutralize H2O2. TrxR reduce sulfhydryl-groups like in cysteins either directly or via their cofactor thioredoxin and thus are involved in protein folding and critical protein-protein and protein-DNA interactions, e.g. modulation of dimerization and/or DNA-binding and ligand binding of transcription factors (glucocorticoid receptor and other steroid receptors, NF kappa B). In addition, the antibiotic peptide NK-lysin was shown to be a substrate for TrxR alpha, suggesting that TrxR protects the cell itself from the cytotoxic effects of NK-lysin. Selenium is incorporated into selenocysteine (Secys) in a regulated fashion in the presence of a hairpin structure (Secis element) in the 3'UTR of selenoprotein genes. Secis elements direct the insertion of Secys at UGA codons, which function as opal stop codons in the absence of a suitable Secis element and in selenium deficiency. The above mentioned processes might therefore be altered in relative selenium deficiency or vice versa be upregulated through selenium supplementation. We have shown that TrxR alpha is a 1.25 (OH)2 vitamin D3-responsive early gene in monocytic cells and that TrxR activity as well as GPx activity in these cells can be upregulated by the addition of selenium in vitro and ex vivo. Recent work demonstrates that thioredoxin rapidly enters the cell nucleus upon treatment of cells with H2O2, but little is known about the compartimentalization of the respiratory burst and the intracellular localization of antioxidant enzymes during that process. Macrophage function is insufficient if the generation of a respiratory burst is altered like in hereditary chronic granulomatous disease on one hand, but on the other hand is as well disturbed, if there is a lack in antioxidant enzyme activity. Thioredoxin has been identified as a lymphocyte growth factor and might therefore be involved in the crosstalk between macrophages and lymphocytes. The relevance of the above mentioned and other yet undefined monocytic selenoproteins remains to be elucidated in detail as well as the relevance of selenium supplementation in nutrition in general and in situations of critical infectious disease and autoimmunity.
  Medizinische Klinik 11/1999; 94 Suppl 3:29-34. · 0.34 Impact Factor
• Article: The selenoprotein thioredoxin reductase is expressed in peripheral blood monocytes and THP1 human myeloid leukemia cells--regulation by 1,25-dihydroxyvitamin D3 and selenite.

  N Schütze, J Fritsche, R Ebert-Dümig, D Schneider, J Köhrle, R Andreesen, M Kreutz, F Jakob
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  ABSTRACT: 1,25(OH)2 Vitamin D3 (1,25(OH)2D3) and adhesion propagate monocyte differentiation. We identified the selenoprotein thioredoxin reductase (TrxR) as a new molecular target for 1,25(OH)2D3 in monocytes during this process. In THP1 monocytic leukemia cells 1,25(OH)2D3 stimulated TrxR mRNA levels 2-4-fold by 4-8 h and enhanced TrxR activity (60%) (as measured by the dithionitrobenzole-assay) after 24 h, which declined below baseline after 96 h. The addition of 100 nM selenite enhanced (approx. 50%) basal and stimulated enzyme activity in THP1 cells. The relative stimulation by 1,25(OH)2D3 was very similar but peak levels were sustained in THP1 cells up to 48 h. Human peripheral blood monocytes (PBM) of different donors showed very low basal TrxR steady state mRNA levels which were markedly enhanced (as analyzed by Northern blotting) after 4 h of adherence to culture dishes. 1,25(OH)2D3 (100 nM) further stimulated TrxR mRNA expression (4 h, 3-fold). TrxR enzyme activity mirrored the mRNA changes. Basal activity was stimulated approx. 25% by adhesion in culture alone and was further stimulated (approximately 15%) by 1,25(OH)2D3 after 4 h. By 24 h similar results were achieved but the effect of 1,25(OH)2D3 could be seen in the presence of 100 nM selenium only. The expression of TrxR and its regulation by 1,25(OH)2D3 and selenite in monocytes might be important for their induction of differentiation and maintenance of function.
  BioFactors 02/1999; 10(4):329-38. · 4.93 Impact Factor
• Article: The thioredoxin reductase/thioredoxin system in cells of the monocyte/macrophage pathway of differentiation.

  R Ebert-Dümig, N Schütze, F Jakob
  BioFactors 01/1999; 10(2-3):227-35. · 4.93 Impact Factor