Synergistic activation of intercellular adhesion molecule 1 (ICAM-1) by TNF-alpha and IFN-gamma is mediated by p65/p50 and p65/c-Rel and interferon-responsive factor Stat1 alpha (p91) that can be activated by both IFN-gamma and IFN-alpha

FEBS Lett. 1994 Nov 7;354(2):220-6. doi: 10.1016/0014-5793(94)01130-3.

Abstract

Human ICAM-1 expression is up-regulated by IFN-gamma and TNF-alpha and synergistically increased by a combination of both. Transient expression of ICAM-1/luciferase constructs led to definition of the regulatory regions mediating the cytokine response and showed that both are necessary for synergism. Immunochemical electromobility shift assays identified the TNF-alpha-dependent complexes that bound to the NF-kappa B like sequence at -187 as p65/p50 and p65/c-Rel. The interferon responsive region at -75 was bound by a Stat1 alpha (p91) containing complex that was activated by both IFN-gamma and IFN-alpha. Although both regions were required for synergism, no additional or enhanced binding complexes were observed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA-Binding Proteins / metabolism*
  • Drug Synergism
  • Fluorescent Antibody Technique
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Interferon-alpha / pharmacology*
  • Interferon-gamma / pharmacology*
  • Luciferases / genetics
  • Melanoma
  • Molecular Sequence Data
  • NF-kappa B / metabolism
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-rel
  • RNA, Messenger / metabolism
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • Regulatory Sequences, Nucleic Acid
  • STAT1 Transcription Factor
  • Trans-Activators / metabolism*
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • DNA-Binding Proteins
  • Interferon-alpha
  • NF-kappa B
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-rel
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Trans-Activators
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • Interferon-gamma
  • Luciferases