Comparative Studies of the Biological Activities of Human Tumor Necrosis Factor and Its Derivatives

Biological activities of human tumor necrosis factor (TNF) and its derivatives were compared. In cytotoxicity assay with L929 cells, one derivative, designated as TNF(Asn), showed significantly lower activity than any other TNF examined. In binding assay, this derivative was also shown to have lower...

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Bibliographic Details
Published in:Journal of biochemistry (Tokyo) 1987, Vol.101 (4), p.919-925
Main Authors: TSUJIMOTO, Masafumi, TANAKA, Shoji, SAKURAGAWA, Yayoi, TSURUOKA, Nobuo, FUNAKOSHI, Kyoko, BUTSUGAN, Tomoko, NAKAZATO, Hiroshi, NISHIHARA, Tatsuro, NOGUCHI, Teruhisa, VILČEK, Jan
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell Division
Cell Survival
Cells, Cultured
Glycoproteins - physiology
Host-tumor relations. Immunology. Biological markers
Humans
Lipoprotein Lipase - antagonists & inhibitors
Medical sciences
Mice
Receptors, Cell Surface - physiology
Receptors, Tumor Necrosis Factor
Recombinant Proteins
Structure-Activity Relationship
Tumor Necrosis Factor-alpha
Tumors
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Summary:Biological activities of human tumor necrosis factor (TNF) and its derivatives were compared. In cytotoxicity assay with L929 cells, one derivative, designated as TNF(Asn), showed significantly lower activity than any other TNF examined. In binding assay, this derivative was also shown to have lower affinity for TNF receptors on L929 cells, suggesting that the cytotoxic activity of TNFs on L929 cells correlates with their affinity for receptors. We also found that the cytotoxic activity of TNF on A673 cells and its inhibitory effect on lipoprotein lipase were parallel with the cytotoxic activity on L929 cells, but the growth-enhancing activity on FS-4 cells and the cytotoxic activity on endothelial cells were not. It was also shown that TNF(Asn) had lower affinity than any other TNF for receptors on these target cells tested. These results suggested that there might be at least two types of cellular responses to TNF; one might correlate with the receptor-binding affinity of TNFs and the other not.
ISSN:0021-924X
1756-2651
DOI:10.1093/oxfordjournals.jbchem.a121960