Transcriptional regulation of intercellular adhesion molecule-1 in astrocytes involves NF-kappaB and C/EBP isoforms

J Neuroimmunol. 1998 Dec 1;92(1-2):196-207. doi: 10.1016/s0165-5728(98)00209-4.


ICAM-1 is an inducible cell surface protein that is involved in cell extravasation into inflamed tissues as well as immune responses. ICAM-1 expression is upregulated by proinflammatory cytokines such as TNF-alpha and IL-1beta in numerous cell types including the astrocyte, which functions as an immune effector cell in the central nervous system (CNS). We investigated the mechanism by which the ICAM-1 gene is transcriptionally regulated in astrocytes in response to TNF-alpha and IL-1beta. Human ICAM-1 promoter constructs linked to the reporter gene luciferase were transiently transfected into astrocytes, stimulated with TNF-alpha and IL-1beta, and ICAM-1 promoter activity examined. We determined that binding sites for both NF-kappaB (-186 bp region) and C/EBP (-198 bp region) are involved in TNF-alpha and IL-1beta-mediated ICAM-1 upregulation. Electrophoretic mobility shift assays using antibodies against NF-kappaB and C/EBP isoforms showed that p65 homodimers and p65/p50 heterodimers bind to the NF-kappaB site, and C/EBPdelta homodimers and C/EBPbeta/delta heterodimers bind to the C/EBP site. Transient transfection assays demonstrated that overexpression of p65 could transactivate the promoter activity of ICAM-1 reporter constructs. p50 overexpression had no effect on the basal levels of ICAM-1 transcription, but inhibited, in a dose dependent manner, p65 mediated transcription. Overexpression of C/EBPbeta slightly inhibited basal levels of ICAM-1 promoter activity, however, when C/EBPbeta and p65 were cotransfected, C/EBPbeta completely abolished the transactivating effects of p65. These results demonstrate that cytokine-induced ICAM-1 expression in astrocytes is regulated by interactions between NF-kappaB and C/EBP transcription factors.

Publication types

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

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Astrocytes / physiology*
  • DNA-Binding Proteins / physiology*
  • Enhancer Elements, Genetic / physiology*
  • Humans
  • Intercellular Adhesion Molecule-1 / drug effects
  • Intercellular Adhesion Molecule-1 / genetics*
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Interleukin-1 / pharmacology
  • Isomerism
  • NF-kappa B / physiology*
  • NF-kappa B p50 Subunit
  • Promoter Regions, Genetic / genetics
  • Rats
  • Transcription Factor RelA
  • Transcription, Genetic / physiology*
  • Tumor Necrosis Factor-alpha / pharmacology


  • DNA-Binding Proteins
  • Interleukin-1
  • NF-kappa B
  • NF-kappa B p50 Subunit
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1