Modulation by interferons of the expression of monocyte complement genes

• Published in: Biochemical journal 1990-06, Vol.268 (2), p.387-392
• Main Authors: Lappin, D F, Birnie, G D, Whaley, K
• Format: Article
• Language: English
• Subjects: Cells, Cultured; Complement C1 Inactivator Proteins - biosynthesis; Complement C1 Inactivator Proteins - genetics; Complement C2 - biosynthesis; Complement C2 - genetics; Complement System Proteins - biosynthesis; Complement System Proteins - genetics; Cycloheximide - pharmacology; Drug Synergism; Gene Expression Regulation; Interferon Type I - pharmacology; Interferon-gamma - pharmacology; Interferons - pharmacology; Kinetics; Monocytes - metabolism; Recombinant Proteins; RNA, Messenger - metabolism
• ISSN: 0264-6021; 1470-8728
• DOI: 10.1042/bj2680387

Interferons-alpha, -beta and -gamma (IFNs-alpha, -beta and -gamma) 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 abundances of their respective mRNAs. IFN-gamma was the most effective at stimulating monocyte C1-inh synthesis, whereas IFN-alpha and IFN-beta 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-gamma-treated monocytes but returned to control levels within 8 h in IFN-alpha-treated and IFN-beta-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-alpha and IFN-beta acted synergistically with IFN-gamma 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-gamma plus IFN-alpha or IFN-beta on C2 synthesis appeared to be additive rather than synergistic. IFN-gamma inhibited synthesis of C3 by monocytes, but IFN-alpha and IFN-beta 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.