Potentiation of Human Interferon Production by Superinduction

Summary

In a human diploid cell line (RSTC-2) actinomycin D treatment (0.03-0.30 µg/ml) before stimulation of interferon by polyriboinosinic-polyribocytidylic acid caused up to a 7-Fold rise in titer over controls not treated with actinomycin D. In cultures induced and incubated in the continuous presence of cycloheximide, there was a 9-fold enhancement in titer, but there was inhibition of interferon production in the presence of puromycin or fluorophenylalanine. In cells treated for 4 hours with puromycin and then washed, there was a 130-fold rise in interferon titers. Both actinomycin treatment and a 4-hour exposure to puromycin gave rise to higher titers than either drug alone. In this system, interferon treatment inhibited interferon production. These results indicate that superinduction of interferon apparently takes place in human cells. A postulated model For interferon induction in human cells involves a repressor protein that binds interferon messenger RNA (mRNA). Superinduction of interferon occurs after addition of inducer when interferon mRNA accumulates without adequate repressor due to treatment with antimetabolites. This superinduction phenomenon may be used to produce high titers of human interferon from diploid cell cultures.