MODULATION BY INTERFERONS OF THE EXPRESSION OF MONOCYTE COMPLEMENT GENES

Interferons-α, -β and γ (IFNs -α, -β and -γ) stimulated the synthesis of the second complement component (C2), Factor B (B) and C1 inhibitor (C1-inh) by human monocytes in vitro. The degree of increase of the secretion rates of C2, B and C1-inh was dose-dependent and proportional to increases in the abundance of their respective mRNAs. IFN-γ was the most effective at stimulating monocyte C1-inh synthesis, whereas IFN-α and IFN-β were marginally more effective at stimulating monocyte C2 and B synthesis. Kinetic studies showed that the effect of the IFNs was rapid, with maximum stimulation occurring within 1-2 h for all three proteins. After the removal of IFNs from cultures the C1-inh mRNA abundance remained elevated for over 24 h in IFN-γ treated monocytes but returned to control levels within 8 h in IFN-α-treated and IFN-β-treated monocytes. The abundances of C2 mRNA and B mRNA also returned to basal values within 8 h after removal of any of the three cytokines from the cultures. Both IFN-α and IFN-β acted synergistically with IFN-γ to stimulate synthesis of C1-inh and B. This synergistic effect only occurred when the cytokines were present in the cultures simultaneously. The effects of IFN-γ plus IFN-α or IFN-β on C2 synthesis appeared to be additive rather than synergistic. IFN-γ inhibited synthesis of C3 by monocytes, but IFN-α and IFN-β had no effect on the synthesis of this protein. Furthermore, none of the three cytokines had any effect on the expression of actin mRNA in monocytes.