In vitro effects of tumor necrosis factor-α on human thyroid follicular cells

Abstract

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.

Expression of tumour necrosis factor-alpha (TNF-α) mRNA and protein in pathological thyroid tissue and carcinoma cell lines

“…Human thyrocytes possess a specific receptor for TNF- [1]. TNF-has been suggested as a possible mediator of increased expression of MHC class I molecules on thyroid epithelial cells in GD.…”

“…The exact role of this cytokine in the pathogenesis of autoimmune thyroid diseases is still unclear. TNF-receptors have been shown on thyroid epithelial cells and FRTL-5 cells, and a multitude of TNF-in vitro actions have been demonstrated on these cells [1][2][3][4][5][6][7].…”

Influence of tumour necrosis factor-α, tumour necrosis factor-β and interferon-γ, separately and added together with interleukin-1 β, on the function of cultured human thyroid cells

“…Their assay system differed from ours in that they used pretreatment with IFN-for 5 days followed by a shortterm (120 min) incubation with TSH. In the study of Kraiem et al (1990), as well as in that of Deuss et al (1992), the augmentation of the acute TSH-induced cAMP production could have been caused by an altered sensitivity of the cells to TSH caused by increased activity of the TSH receptor/adenylate-cyclase system following inhibition of the metabolic pathways induced by longterm exposure to IFN-or TNF-. In contrast, our study describes the simultaneous effects of TSH and the cyto¬ kines.…”

Proinflammatory Mediators and Genetic Background in Oncogene Mediated Tumor Progression

“…For instance, low level cytokine production by thyrocytes can directly stimulate, in a paracrine or autocrine fashion, the growth of thyroid cells (18,19) via the secretion of Il1␣ (20), Il6 (21), or IL4 and IL10 (17). Moreover, previous work has demonstrated that RET/PTC3 (RP3) can directly induce the production of these and other inflammatory factors (12) and, when such cells are transplanted into mice, induce the attraction of activated macrophages.…”