Lappin D F, Birnie G D, Whaley K
University Department of Pathology, Western Infirmary, Glasgow, Scotland.
Eur J Biochem. 1990 Nov 26;194(1):177-84. doi: 10.1111/j.1432-1033.1990.tb19443.x.
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.
在体外单核细胞培养物中添加淋巴母细胞样干扰素α、成纤维细胞干扰素β和重组干扰素γ，可使编码补体第二成分（C2）、B因子（B）和C1抑制剂的基因转录率呈剂量依赖性增加，以及它们各自mRNA的丰度增加。干扰素γ在刺激C1抑制剂基因转录方面最有效，而干扰素α和β在增加C2和B基因转录方面更有效。干扰素γ可降低C3基因的转录。这些细胞因子均未改变肌动蛋白基因的转录水平。干扰素诱导的C2、B和C1抑制剂基因转录水平变化迅速，在接触这些细胞因子后30分钟内就会出现显著变化。从培养液中去除干扰素4小时内，C1抑制剂、C2、B和C3基因的转录水平恢复到对照值，C2、B和C3 mRNA的丰度也恢复到对照值。然而，在干扰素γ处理的单核细胞中，C1抑制剂mRNA的丰度仍保持升高。干扰素组合对C2、B和C1抑制剂基因转录的刺激作用小于相加效应，而C1抑制剂mRNA和B mRNA的测量结果表明，干扰素γ与干扰素γ协同作用可增加mRNA的丰度。它们对C2 mRNA丰度的影响小于相加效应。干扰素α未改变C1抑制剂、C2、B和C3 mRNA的半衰期，而干扰素γ使C2 mRNA的半衰期缩短约50%，使B和C1抑制剂mRNA的半衰期分别延长约两倍和五倍。干扰素对C3 mRNA的半衰期均无影响。这些结果表明，在干扰素γ处理的单核细胞中发生的C1抑制剂合成大量增加，是转录增加和C1抑制剂mRNA稳定性增加共同作用的结果。它们还表明，干扰素α与干扰素γ对C1抑制剂和B因子合成的协同作用也依赖于转录增加和mRNA稳定性增加。
