Interferon-alpha, -beta, and -gamma augment the levels of rRNA precursors in peritoneal macrophages but not in macrophage cell lines and fibroblasts.

We have studied the ribosomal RNA content in murine peritoneal macrophages activated to cytotoxicity with interferon-alpha (IFN-alpha), interferon-beta (IFN-beta), and interferon-gamma (IFN-gamma). Total RNA was purified from IFN-alpha, -beta, or -gamma activated macrophages, and Northern blot analysis was performed by using subcloned fragments specific for precursor rRNA (pre-rRNA) as probes. All types of interferon (alpha, beta, gamma) at the doses normalized for induction of cytotoxic activity caused accumulation of 45S, 41S, and 36S pre-rRNA. In contrast, the levels of 32S pre-RNA and 28S, 5.8S, and 18S mature rRNA were not affected by IFN treatment. Therefore, the accumulation of pre-rRNA in macrophages activated to cytotoxicity by IFN was not paralleled by changes in total content of mature rRNA. No accumulation of pre-rRNA upon IFN treatment was found in a murine fibroblast cell line (L929 cells) or in a macrophage cell line (GG2EE) immortalized from bone marrow of C3H/HeJ mice. Neither of those cell lines become cytotoxic in response to IFN. Overall, our data support the concept that IFN acts selectively on the mechanism controlling the levels of some pre-rRNA and that the mechanism of IFN action involves the post-transcriptional control of ribosomal gene expression.