Modulation by interferons of the expression of monocyte complement genes.
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.
University of Glasgow Department of Pathology, Western Infirmary, Glasgow, U.K.
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Lappin
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Birnie
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Whaley
D002478:Cells, Cultured; D003174:Complement C1 Inactivator Proteins / Q000096:biosynthesis / Q000235:genetics*; D003175:Complement C2 / Q000096:biosynthesis / Q000235:genetics; D003165:Complement System Proteins / Q000096:biosynthesis / Q000235:genetics*; D003513:Cycloheximide / Q000494:pharmacology; D004357:Drug Synergism; D005786:Gene Expression Regulation; D007370:Interferon Type I / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007372:Interferons / Q000494:pharmacology*; D007700:Kinetics; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D011994:Recombinant Proteins
D003174:Complement C1 Inactivator Proteins; D003175:Complement C2; D007370:Interferon Type I; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007371:Interferon-gamma; D003165:Complement System Proteins; D007372:Interferons; D003513:Cycloheximide