Consensus interferon induces peak mRNA accumulation at lower concentrations than interferon-alpha 2a.
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.
Klein
S B
SB
Department of Biology, Indiana University, Bloomington 47405.
Blatt
L M
LM
Taylor
M W
MW
D000595:Amino Acid Sequence; D016384:Consensus Sequence; D015870:Gene Expression; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D007370:Interferon Type I / Q000737:chemistry / Q000235:genetics*; D016898:Interferon-alpha / Q000737:chemistry / Q000235:genetics*; D007700:Kinetics; D012333:RNA, Messenger / Q000378:metabolism*; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D006684:HLA-DR Antigens; D007370:Interferon Type I; D016898:Interferon-alpha; D012333:RNA, Messenger; D011994:Recombinant Proteins