Dexamethasone inhibits feedback regulation of the mitogenic activity of tumor necrosis factor, interleukin-1, and epidermal growth factor in human fibroblasts

✍ Scribed by Dr. Masayoshi Kohase; Dorothy Henriksen-Destefano; Pravinkumar B. Sehgal; Jan Vilĉek

• Publisher: John Wiley and Sons
• Year: 1987
• Tongue: English
• Weight: 900 KB
• Volume: 132
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041320211

✦ Synopsis

Tumor necrosis factor (TNF), interleukin-I (IL-I), and epidermal growth factor (EGF) were mitogenic for human diploid FS-4 fibroblasts. Dexamethasone amplified the growth-stimulating action of all three agents. Amplification of the growth-stimulating action was maximal when dexamethasone was added along with TNF or EGF; no amplification was seen if the addition of dexamethasone was delayed for more than 3 hr. Prolonged simultaneous treatment with TNF and EGF resulted in less growth stimulation than treatment with EGF alone. Dexamethasone abolished this apparent antagonistic interaction between TNF and EGF. Dexarnethasone also inhibited the antiviral action of TNF against encephalomyocarditis (EMC) virus in FS-4 cells. TNF and IL-I increased the steady state level of interferon (IFN)-beta, mRNA but failed to induce detectable levels of IFN-betal mRNA in FS-4 cells. Dexamethasone inhibited the increase of IFN-beta2 mRNA levels by IL-1 or TNF. Inhibition of IFN-beta synthesis is likely to be responsible for t h e inhibition of the TNFinduced antiviral state by dexamethasone. Since IFNs suppress cell growth, inhibition of endogenous IFN-beta synthesis may also be responsible for the amplification by dexamethasone of the growth-stimulating action of TNF and 11-1. Amplification of the mitogenic action of EGF by dexamethasone appears to be mediated by a different mechanism.