Interferon-induced transcriptional and post-transcriptional modulation of factor H and C4 binding-protein synthesis in human monocytes.
Cultured human monocytes synthesize factor H (H) and C4 binding protein (C4-bp), as assessed by measuring their presence in culture fluids, and demonstrating the presence of their corresponding mRNAs in total monocyte RNA by Northern blot analysis and by nuclear run-on experiments. H mRNA (4.3 kb and 1.8 kb) could only be detected when cycloheximide (2.5 micrograms/ml) was present in monocyte culture fluid. Recombinant interferon-gamma (IFN-gamma) and lymphoblastoid interferon-alpha (IFN-alpha) produce dose-related increases in the synthesis of H and C4-bp and in the abundance of C4-bp mRNA (2.5 kb). Increased abundance of H mRNA was also seen when cycloheximide (2.5 micrograms/ml) was present in the cultures. Both cytokines increased the transcription rates of the H and C4-bp genes. These changes in transcription were rapid, with significant increases being observed within 30 min of exposure. Following the removal of the cytokines from the cultures the transcription rates of both genes returned to control levels within 4 h. The effects of combining IFN-alpha and IFN-gamma on H and C4-bp transcription rates, mRNA abundances and protein secretion rates were not quantitatively additive. The half-life of H mRNA in monocytes was 15 min, whereas that of C4-bp mRNA was 2 h 45 min. Neither half-life was altered by IFN-gamma.
University Department of Pathology, Western Infirmary, Glasgow, Scotland, U.K.
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Lappin
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Whaley
D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D003180:Complement C3b Inactivator Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D017242:Complement Factor H; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016167:Integrin alphaXbeta2; D007370:Interferon Type I / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007372:Interferons / Q000494:pharmacology*; D007700:Kinetics; D009000:Monocytes / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*
C493495:CFH protein, human; D002352:Carrier Proteins; D003180:Complement C3b Inactivator Proteins; D016167:Integrin alphaXbeta2; D007370:Interferon Type I; D012333:RNA, Messenger; D017242:Complement Factor H; D007371:Interferon-gamma; D007372:Interferons