Stabilization of the bioactivity of tumor necrosis factor by its soluble receptors.
Stabilization of the bioactivity of tumor necrosis factor by its soluble receptors.
复制标题
肿瘤坏死因子的生物活性因子的可溶受体的稳定性。
DOI：
10.1084/jem.175.2.323
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发表时间：
1992-02-01
期刊：
影响因子：
--
通讯作者：
Wallach D
中科院分区：
文献类型：
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作者：
Aderka D;Engelmann H;Maor Y;Brakebusch C;Wallach D
肿瘤坏死因子受体以细胞相关和可溶性形式存在，两者都与肿瘤坏死因子特异性结合。由于可溶性形式的肿瘤坏死因子受体(sTNF-R)能与细胞相关的肿瘤坏死因子受体竞争肿瘤坏死因子，因此被认为具有抑制肿瘤坏死因子活性的作用；在高浓度时，可溶型肿瘤坏死因子受体确实抑制肿瘤坏死因子的作用。然而，我们在此报道，在低浓度的sTNF-R存在下，其诱导依赖于这种细胞因子的长期治疗的TNF的作用被增强，反映了自发的TNF活性下降的sTNF-R的减弱。有证据表明，sTNF-Rs对肿瘤坏死因子活性的稳定源于其与sTNF-Rs形成的复合体内的结构稳定，这表明sTNF-Rs不仅可以通过干扰其与细胞的结合而影响其活性，还可以通过稳定其结构和保持其活性来影响其活性，从而增强其某些作用。
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.