Tumor necrosis factor-α is assumed to be an important mediator in thyroid autoimmunity. In the present study we have shown that human thyrocytes possess a single specific binding site for recombinant tumor necrosis factor-α with an average of 9,300 receptors/cell (Kd = 1.9 · 10−10 mol). The effects of the cytokine on thyroid cell proliferation were assessed by 3H-thymidine uptake as well as by the protein and DNA content of cell monolayers. Low dose tumor necrosis factor-α resulted in a moderate stimulation of cell proliferation with an increase of 3H-thymidine incorporation from 44,613±7,989 cpm under basal conditions to 63,326±6,822 cpm after 100 U/l tumor necrosis factor-α (p <0.01). Higher doses of the cytokine were less effective. On average, bTSH stimulated cAMP production of human thyrocytes was significantly augmented after preincubation with recombinant tumor necrosis factor-α. The maximum effect was observed after 1,000 U/l tumor necrosis factor-α (281.5±107.0 vs 114.5±33.6 fmol cAMP/μg protein under basal conditions; p<0.05), whereas higher doses of the cytokine were again less effective. This phenomenon could at least partly be explained by a cytokine-mediated downregulation of tumor necrosis factor-α binding. We conclude that in vitro tumor necrosis factor-α modulates in addition to its well known synergistic effect on interferon-γ induced HLA class II expression the function and proliferation of human thyroid follicular cells as well. These effects are mediated via specific cell surface receptors.
Cytostatic and Cytotoxic Effects of Recombinant Tumor Necrosis Factor-α on Sensitive Human Melanoma Cells In Vitro May Result in Selection of Cells with Enhanced Markers of Malignancy
