Interferon-γ modulates retinoblastoma gene mrna in monocytoid cells

To study the effect of interferon gamma (IFN-_γ) on the expression of the retinoblastoma (RB) susceptibility gene, we performed Northern-blot analysis on RNA extracted from Wish, HEL and monocytoid cell lines U-937 and THP-I treated with 1,000 IU/ml of recombinant IFN-_γ. In U-937 and THP-I cells, IFN-_γ increased the abundance of RB mRNA. In Wish and HEL cells, co-treatment with cycloheximide was required for IFN-_γ to increase the level of RB mRNA. Pre-treatment THP-I cells with cycloheximide prior to IFN-_y treatment augmented the effects of IFN-_γ on RB gene expression. The effect of IFN-_γ in THP-I cells was observed after 3 hr treatment, being more pronounced after 6 hr and persisting until at least 18 hr, although at a lower level. These results suggest that IFN-_γ regulates the level of RB mRNA by different mechanisms in the different cell types. This cytokine increases the abundance of RB mRNA in monocytoid cell lines, reinforced by prior treatment with cycloheximide. Inhibition of protein synthesis is required in Wish and HEL cell lines before IFN-_γ has an effect on RB gene expression.