Functional Equivalents of Interferon-Mediated Signals Needed for Induction of an mRNA Can Be Generated by Double-Stranded RNA and Growth Factors

EMBO J. 1987 Nov;6(11):3373-8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Line
  • Epidermal Growth Factor / pharmacology
  • Growth Substances / pharmacology*
  • HeLa Cells / drug effects
  • HeLa Cells / metabolism
  • Humans
  • Interferon Type I / pharmacology*
  • Interferon-gamma / pharmacology*
  • Platelet-Derived Growth Factor / pharmacology
  • Poly I-C / pharmacology
  • RNA, Double-Stranded / genetics*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / drug effects*
  • RNA, Messenger / genetics
  • Transcription, Genetic / drug effects*
  • Vesicular stomatitis Indiana virus / genetics

Substances

  • Growth Substances
  • Interferon Type I
  • Platelet-Derived Growth Factor
  • RNA, Double-Stranded
  • RNA, Messenger
  • Epidermal Growth Factor
  • Interferon-gamma
  • Poly I-C