Characterization of receptors for human tumour necrosis factor and their regulation by γ-interferon
- 19 December 1985
- journal article
- letter
- Published by Springer Science and Business Media LLC in Nature
- Vol. 318 (6047), 665-667
- https://doi.org/10.1038/318665a0
Abstract
Tumour necrosis factors, TNF-α and TNF-β (previously called lymphotoxin), are the products of activated monocytes and lymphocytes, respectively, and both have recently been purified, sequenced and cloned by recombinant DNA methods1–5, revealing 35% identity and 50% homology in the amino-acid sequence. Both proteins have been found to be specifically toxic to many tumour cells. Furthermore, it has been reported that various interferons are synergistic with TNF for anti-tumour effects in vitro6–8, while activities attributed to the two proteins have also been shown to necrotize various tumours in vivo2,3,9. We have now prepared 125I-labelled highly purified recombinant human TNF-α to study in detail its binding to the human cervical carcinoma cell line ME-180. Our results indicate that there is a single class of specific high-affinity receptors for TNF on this cell line which has a Kd of about 0.2 nM and an average of 2,000 receptor sites per cell. The binding of labelled TNF-α to these cells can be inhibited by both TNF-α and TNF-β but not by γ-interferon (IFN-γ). However, preincubation of cells with IFN-γ increases the total number of TNF receptors two to threefold without any significant change in the affinity constant. This is the first report that TNF-α and -β share a common receptor and that the receptors can be up-regulated by interferon. Our results may explain previous observations regarding similar biological activities observed for these two cytotoxic proteins and also their synergistic action with interferons.Keywords
This publication has 18 references indexed in Scilit:
- Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxinNature, 1984
- Cloning and expression of cDNA for human lymphotoxin, a lymphokine with tumour necrosis activityNature, 1984
- Interrelationships of human interferon-gamma with lymphotoxin and monocyte cytotoxin.The Journal of Experimental Medicine, 1984
- Chemical and Biological Properties of Human LymphotoxinPublished by Springer Science and Business Media LLC ,1984
- Platelet-derived growth factor binds specifically to receptors on vascular smooth muscle cells and the binding becomes nondissociable.Proceedings of the National Academy of Sciences of the United States of America, 1982
- Characterization of corticotropin receptors on adrenocortical cells.Proceedings of the National Academy of Sciences of the United States of America, 1981
- Evidence that types I and II interferons have different receptorsNature, 1981
- Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphenylglycolurilBiochemical and Biophysical Research Communications, 1978
- An endotoxin-induced serum factor that causes necrosis of tumors.Proceedings of the National Academy of Sciences of the United States of America, 1975
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970