Regulation of intercellular adhesion molecule-1 gene expression by tumor necrosis factor-alpha, interleukin-1 beta,

P Shrikant1, I Y Chung, M E Ballestas

  • 1Department of Cell Biology, University of Alabama at Birmingham 35294.

Insights

Proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1 beta, and interferon-gamma enhance intercellular adhesion molecule-1 (ICAM-1) expression in astrocytes. This suggests astrocytes contribute to central nervous system inflammation.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Astrocytes, the primary glial cells in the central nervous system (CNS), express Intercellular Adhesion Molecule-1 (ICAM-1).
  • ICAM-1 plays a role in cell adhesion and immune responses within the CNS.

Purpose of the Study:

  • To investigate the effects of key proinflammatory cytokines on ICAM-1 expression in primary rat astrocytes.
  • To determine the potency and kinetics of cytokine-induced ICAM-1 expression.
  • To elucidate the regulatory mechanisms, including gene transcription and mRNA stability, controlling ICAM-1 expression.

Main Methods:

  • Primary rat astrocytes were treated with tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interferon-gamma (IFN-gamma).
  • Quantitative analysis of ICAM-1 mRNA and protein expression was performed using various time points.
  • Nuclear run-on assays and mRNA stability studies were conducted to assess gene transcription and mRNA half-life.

Main Results:

  • All three cytokines (TNF-alpha, IL-1 beta, IFN-gamma) significantly enhanced ICAM-1 mRNA and protein expression in astrocytes.
  • TNF-alpha was the most potent inducer, followed by IL-1 beta, then IFN-gamma.
  • Cytokine treatment enhanced ICAM-1 gene transcription, with modest effects on mRNA stability. Peak protein expression occurred 12-24 hours post-treatment.

Conclusions:

  • Astrocytes can be induced to express ICAM-1 by proinflammatory cytokines under conditions mimicking CNS inflammation.
  • Upregulated ICAM-1 expression on astrocytes likely contributes to inflammatory cell recruitment and exacerbation of CNS inflammatory diseases like MS and EAE.

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