Effects of tumor necrosis factor and interferon-beta on proliferation and epidermal growth factor binding in young and senescent WI-38 cells.
Tumor necrosis factor-alpha (TNF) and various interferons (IFN) have potent cytostatic or cytotoxic effects on a variety of human tumor-derived cell lines. Their effects on normal cells are more controversial. We have examined the effects of TNF and IFN-beta on the proliferation of WI-38 cells in a serum-free, growth factor-supplemented medium and in serum-containing medium. These cells respond to the combination of epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), and dexamethasone by DNA synthesis at a rate and extent equivalent to serum-stimulated cells. TNF has no effect on this growth factor-stimulated proliferation. However, it is stimulatory in serum-containing medium. IFN-beta inhibits DNA synthesis 60 to 70% in both young and senescent cells. TNF and IFN-beta together have a synergistic effect and completely inhibit growth factor-stimulated DNA synthesis in young cells. No synergism was observed with senescent cells. TNF stimulated an increase in the number of EGF specific binding sites two- to threefold in 24 h in both young and senescent cells. This seems to result from a proportional increase in a very high affinity binding site. IFN-beta has little or no effect on EGF binding either alone or in combination with TNF.
Cianciarulo
F L
FL
Wistar Institute, Philadelphia, Pennsylvania 19104.
Phillips
P D
PD
Cristofalo
V J
VJ
D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D016922:Cellular Senescence; D004261:DNA Replication / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D007700:Kinetics; D008168:Lung; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D004815:Epidermal Growth Factor; D016899:Interferon-beta; D003907:Dexamethasone; D066246:ErbB Receptors