Interleukin-6 activates and regulates transcription factors of the interferon regulatory factor family in M1 cells

J Biol Chem. 1993 Apr 25;268(12):9092-7.

Abstract

Activation of (2'-5') A synthetase gene expression in interleukin-6 (IL-6)-treated myeloleukemic M1 cells correlates with protein binding to the interferon response sequence enhancer (IRS). A new interferon response sequence complex, F6, is induced by IL-6 independently of interferon and is identified here as comprising the interferon regulatory factor-1 (IRF-1) and IRF-2, by use of specific antibodies in DNA mobility shift assays with probes containing IRF binding sites. IRF-1 and IRF-2 have, respectively, positive and negative transcriptional effects on interferon-beta and interferon-inducible genes. In the IL-6-treated M1or cells, IRF-1 binding is activated early and maximally at 1 h, whereas the onset of IRF-2 binding is delayed. In a cell variant M1res, where (2'-5') A synthetase is no more induced, IRF-2 binding is constitutive, and IRF-1 binding is not seen before or after IL-6 treatment. In sensitive M1or cells, IL-6 rapidly induces IRF-1 mRNA, but in M1res cells, IRF-1 mRNA is constitutively high and not changed by IL-6. IRF-2 mRNA levels are also constitutive and not inducible by IL-6 even in M1or cells. The dissociation between induction of mRNAs and of protein binding observed suggests that the activity of the IRF proteins is regulated by IL-6. Transcripts of a third member of the IRF gene family, ICSBP, encoding a protein known to act as repressor, were found to be strongly down-regulated by IL-6. The rapid activation of IRF-1 and the modulation of the other transcription factors of this family may play a role in the early phase of IL-6 action on the M1 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Blotting, Northern
  • CHO Cells
  • Cell Line
  • Cricetinae
  • DNA
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Enhancer Elements, Genetic
  • Humans
  • Interferon Regulatory Factor-1
  • Interferon Regulatory Factor-2
  • Interleukin-6 / physiology*
  • Kinetics
  • Mice
  • Molecular Sequence Data
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • RNA, Messenger / metabolism
  • Repressor Proteins*
  • Transcription Factors / metabolism*
  • Transcription, Genetic*

Substances

  • DNA-Binding Proteins
  • IRF1 protein, human
  • IRF2 protein, human
  • Interferon Regulatory Factor-1
  • Interferon Regulatory Factor-2
  • Interleukin-6
  • Irf1 protein, mouse
  • Irf2 protein, mouse
  • Phosphoproteins
  • RNA, Messenger
  • Repressor Proteins
  • Transcription Factors
  • DNA