PMID: 1310100Feb 1, 1992

Stabilization of the bioactivity of tumor necrosis factor by its soluble receptors

The Journal of Experimental Medicine
D AderkaD Wallach

Abstract

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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Tumor Necrosis Factor-alpha
Tumor Necrosis Factor Receptor
Hormone Receptors, Cell Surface
Proteins, Recombinant DNA
Cell Density
Fibroblasts
Tumor Cells, Cultured
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Enzyme-Linked Immunosorbent Assay
Chronic Lymphocytic Leukemia

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