Klein S B, Blatt L M, Taylor M W
Department of Biology, Indiana University, Bloomington 47405.
J Interferon Res. 1993 Oct;13(5):341-7. doi: 10.1089/jir.1993.13.341.
The biological activity of a novel recombinant interferon, r-metIFN-con1, which represents a consensus sequence of the most commonly appearing amino acids at each locus of 14 naturally occurring IFN-alpha s, was assessed and compared to that of IFN-alpha 2a. The increase in cellular mRNA levels for three IFN-inducible genes served as a quantitative measure of the effectiveness of the stimulation by each of the IFNs. Three cell lines were treated with equimolar amounts of two IFNs encompassing a 5 log range and mRNA was extracted at five different times after treatment. In all cases, r-metIFN-con1 produced mRNA increases at lower concentrations than IFN-alpha 2a. HLA-DR alpha mRNA, which is not affected by IFN-alpha in ME180 or Daudi cells, was also not affected by r-metIFN-con1. However, in Eskol cells, both IFNs effected an increase in HLA-DR alpha mRNA to similar levels. The r-metIFN-con1 was effective at approximately 10-fold lower molar concentrations. At effective concentrations (10-fold lower molar dose of r-metIFN-con1), both IFNs produced similar kinetics of accumulation of all three mRNAs tested. r-metIFN-con1 is therefore more effective than IFN-alpha 2a at the level of mRNA regulation as well as the antiviral and antiproliferative activities that have been reported previously.
一种新型重组干扰素r-metIFN-con1的生物活性得到了评估,该干扰素代表了14种天然存在的α干扰素在每个位点最常见氨基酸的共有序列,并与α干扰素2a的生物活性进行了比较。三种干扰素诱导基因的细胞mRNA水平升高被用作衡量每种干扰素刺激有效性的定量指标。用等摩尔量的两种干扰素处理三种细胞系,浓度范围跨越5个对数单位,并在处理后的五个不同时间提取mRNA。在所有情况下,r-metIFN-con1在比α干扰素2a更低的浓度下就能使mRNA增加。在ME180或Daudi细胞中不受α干扰素影响的HLA-DRα mRNA,也不受r-metIFN-con1影响。然而,在Eskol细胞中,两种干扰素都能使HLA-DRα mRNA增加到相似水平。r-metIFN-con1在大约低10倍的摩尔浓度下仍有效。在有效浓度下(r-metIFN-con1的摩尔剂量低10倍),两种干扰素对所有三种测试mRNA的积累产生相似的动力学。因此,在mRNA调节水平以及先前报道的抗病毒和抗增殖活性方面,r-metIFN-con1比α干扰素2a更有效。