INTERFERON-MEDIATED TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL MODULATION OF COMPLEMENT GENE-EXPRESSION IN HUMAN MONOCYTES

The addition of lymphoblastoid interferon α, fibroblast interferon β and recombinant interferon γ to in vitro monocyte cultures produced dose‐dependent increases in transcription rates of the genes encoding the second component of complement (C2), factor B (B) and C1 inhibitor, and the abundance of their respective mRNA. Interferon γ was the most effective at stimulating transcription of the C1‐inhibitor gene whereas interferons α and β were more effective at increasing the transcription of the C2 and B genes. Transcription of the C3 gene was reduced by interferon γ. None of these cytokines altered the level of transcription of the actin gene. Interferon‐induced changes in the levels of transcription of the C2, B and C1‐inhibitor genes occurred rapidly, with significant changes occurring within 30 min of exposure to these cytokines. Within 4 h of removal of the interferons from the culture fluid, the level of transcription of the C1‐inhibitor, C2, B and C3 genes returned to control values, as did abundance of C2, B and C3 mRNA. However, the abundance of C1‐inhibitor mRNA remained elevated in interferon‐γ‐treated monocytes. Combinations of interferons produced less than additive effects on the stimulation of the transcription of C2, B and C1‐inhibitor genes, whereas measurements of C1‐inhibitor mRNA and B mRNA showed that interferon γ acted synergistically with interferon γ to increase the abundance of the mRNA. Their effects on C2 mRNA abundance were less than additive. The half‐lives of C1‐inhibitor, C2, B and C3 mRNA were not altered by interferon α, whereas interferon γ shortened the half‐life of C2 mRNA by approximately 50%, and prolonged the half‐lives of B and C1‐inhibitor mRNA approximately twofold and fivefold, respectively. The half‐lives of C3 mRNA was unaltered by either interferon. These results show that the large increase in C1‐inhibitor synthesis which occurs in interferon‐γ‐treated monocytes, is due to a combination of increased transcription and increased C1‐inhibitor mRNA stability. They also suggest that the synergistic effects of interferon α together with interferon γ on C1‐inhibitor and factor B synthesis is also dependent upon increased transcription and increased mRNA stability. Copyright © 1990, Wiley Blackwell. All rights reserved