Interferon-mediated transcriptional and post-transcriptional modulation of complement gene expression in human monocytes

Lappin, D.F., Birnie, G.D. and Whaley, K. (1990) Interferon-mediated transcriptional and post-transcriptional modulation of complement gene expression in human monocytes. European Journal of Biochemistry, 194(1), pp. 177-184. (doi: 10.1111/j.1432-1033.1990.tb19443.x)

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The addition of lymphoblastoid interferon alpha, fibroblast interferon beta and recombinant interferon gamma to in vitro monocyte cultures produced dose-dependent increases in transcription rates of the genes encoding the second component of complement (C2), factor B (B) and C1 inhibitor, and the abundance of their respective mRNA. Interferon gamma was the most effective at stimulating transcription of the C1-inhibitor gene whereas interferons alpha and beta were more effective at increasing the transcription of the C2 and B genes. Transcription of the C3 gene was reduced by interferon gamma. None of these cytokines altered the level of transcription of the actin gene. Interferon-induced changes in the levels of transcription of the C2, B and C1-inhibitor genes occurred rapidly, with significant changes occurring within 30 min of exposure to these cytokines. Within 4 h of removal of the interferons from the culture fluid, the level of transcription of the C1-inhibitor, C2, B and C3 genes returned to control values, as did abundance of C2, B and C3 mRNA. However, the abundance of C1-inhibitor mRNA remained elevated in interferon-gamma-treated monocytes. Combinations of interferons produced less than additive effects on the stimulation of the transcription of C2, B and C1-inhibitor genes, whereas measurements of C1-inhibitor mRNA and B mRNA showed that interferon gamma acted synergistically with interferon gamma to increase the abundance of the mRNA. Their effects on C2 mRNA abundance were less than additive. The half-lives of C1-inhibitor, C2, B and C3 mRNA were not altered by interferon alpha, whereas interferon gamma shortened the half-life of C2 mRNA by approximately 50%, and prolonged the half-lives of B and C1-inhibitor mRNA approximately twofold and fivefold, respectively. The half-life of C3 mRNA was unaltered by either interferon. These results show that the large increase in C1-inhibitor synthesis which occurs in interferon-gamma-treated monocytes, is due to a combination of increased transcription and increased C1-inhibitor mRNA stability. They also suggest that the synergistic effects of interferon alpha together with interferon gamma on C1-inhibitor and factor B synthesis is also dependent upon increased transcription and increased mRNA stability.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Lappin, Dr David
Authors: Lappin, D.F., Birnie, G.D., and Whaley, K.
Subjects:Q Science > QR Microbiology > QR180 Immunology
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
Journal Name:European Journal of Biochemistry
ISSN (Online):1432-1033

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