TY - JOUR
T1 - Stabilization of the bioactivity of tumor necrosis factor by its soluble receptors.
AU - Aderka, D
AU - Engelmann, H
AU - Maor, Y
AU - Brakebusch, C
AU - Wallach, D
N1 - Keywords: Cell Count; Cells, Cultured; Chromatography, Gel; Enzyme-Linked Immunosorbent Assay; Fibroblasts; Humans; Kinetics; Leukemia, Lymphocytic, Chronic, B-Cell; Receptors, Cell Surface; Receptors, Tumor Necrosis Factor; Recombinant Proteins; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha
PY - 1992
Y1 - 1992
N2 - The receptors for tumor necrosis factor (TNF) exist in cell-associated as well as soluble forms, both binding specifically to TNF. Since the soluble forms of TNF receptors (sTNF-Rs) can compete with the cell-associated TNF receptors for TNF, it was suggested that they function as inhibitors of TNF activity; at high concentrations, the sTNF-Rs indeed inhibit TNF effects. However, we report here that in the presence of low concentrations of the sTNF-Rs, effects of TNF whose induction depend on prolonged treatment with this cytokine are augmented, reflecting an attenuation by the sTNF-Rs of spontaneous TNF activity decay. Evidence that this stabilization of TNF activity by the sTNF-Rs follows from stabilization of TNF structure within the complexes that TNF forms with the sTNF-Rs is presented here, suggesting that the sTNF-Rs can affect TNF activity not only by interfering with its binding to cells but also by stabilizing its structure and preserving its activity, thus augmenting some of its effects.
AB - The receptors for tumor necrosis factor (TNF) exist in cell-associated as well as soluble forms, both binding specifically to TNF. Since the soluble forms of TNF receptors (sTNF-Rs) can compete with the cell-associated TNF receptors for TNF, it was suggested that they function as inhibitors of TNF activity; at high concentrations, the sTNF-Rs indeed inhibit TNF effects. However, we report here that in the presence of low concentrations of the sTNF-Rs, effects of TNF whose induction depend on prolonged treatment with this cytokine are augmented, reflecting an attenuation by the sTNF-Rs of spontaneous TNF activity decay. Evidence that this stabilization of TNF activity by the sTNF-Rs follows from stabilization of TNF structure within the complexes that TNF forms with the sTNF-Rs is presented here, suggesting that the sTNF-Rs can affect TNF activity not only by interfering with its binding to cells but also by stabilizing its structure and preserving its activity, thus augmenting some of its effects.
M3 - Journal article
C2 - 1310100
SN - 0022-1007
VL - 175
SP - 323
EP - 329
JO - The Journal of Experimental Medicine
JF - The Journal of Experimental Medicine
IS - 2
ER -