Functional equivalents of interferon-mediated signals needed for induction of an mRNA can be generated by double-stranded RNA and growth factors.
In our earlier studies we demonstrated that in HeLaM cells, interferon-alpha produces two functionally distinguishable signals, both of which are needed for induced transcription of mRNA 561 and other inducible mRNAs. Interferon-gamma cannot induce mRNA 561 because it produces only signal 1. Here we report that platelet-derived growth factor or epidermal growth factor could also produce signal 1. On the other hand, signal 2, which can be produced by interferon-alpha but not by interferon-gamma, could be elicited also by double-stranded RNA. Several lines of evidence suggest that the production of signal 2 by double-stranded RNA was not mediated through interferon. Interferon-induced transcription of mRNA 561 in HeLaM cells or in human fibroblast GM2767 cells was transient. However, in interferon-alpha-treated GM2767 cells, which had ceased to synthesize mRNA 561, transcription of this mRNA could be induced effectively by double-stranded RNA suggesting that this induction process could bypass the interferon-mediated down-regulation of induced transcription. Unlike HeLaM and GM2767 cells, in Daudi cells, induction of mRNA 561 by interferon-alpha was not transient. Transcription of this and two other induced mRNAs continued at a high rate even after 18 h of interferon-alpha treatment of these cells. The lack of down-regulation of interferon-induced gene expression may be responsible for interferon's acute antigrowth effects on these cells.
Tiwari
R K
RK
Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Kusari
J
J
Sen
G C
GC
D002460:Cell Line; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics
D006133:Growth Substances; D007370:Interferon Type I; D010982:Platelet-Derived Growth Factor; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D007371:Interferon-gamma; D011070:Poly I-C