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.
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1 February 1992
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February 01 1992
Stabilization of the bioactivity of tumor necrosis factor by its soluble receptors.
D Aderka,
D Aderka
Department of Medicine T, Tel-Aviv Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
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H Engelmann,
H Engelmann
Department of Medicine T, Tel-Aviv Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
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Y Maor,
Y Maor
Department of Medicine T, Tel-Aviv Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
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C Brakebusch,
C Brakebusch
Department of Medicine T, Tel-Aviv Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
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D Wallach
D Wallach
Department of Medicine T, Tel-Aviv Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
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D Aderka
Department of Medicine T, Tel-Aviv Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
H Engelmann
Department of Medicine T, Tel-Aviv Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
Y Maor
Department of Medicine T, Tel-Aviv Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
C Brakebusch
Department of Medicine T, Tel-Aviv Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
D Wallach
Department of Medicine T, Tel-Aviv Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1992) 175 (2): 323–329.
Citation
D Aderka, H Engelmann, Y Maor, C Brakebusch, D Wallach; Stabilization of the bioactivity of tumor necrosis factor by its soluble receptors.. J Exp Med 1 February 1992; 175 (2): 323–329. doi: https://doi.org/10.1084/jem.175.2.323
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