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.
Lappin
D F
DF
University of Glasgow Department of Pathology, Western Infirmary, Glasgow, U.K.
Birnie
G D
GD
Whaley
K
K
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