Regulation of intercellular adhesion molecule-1 gene expression by tumor necrosis factor-α, interleukin-1β, and interferon-γ in astrocytes

Protul Shrikant, Yup Chung Il Yup Chung, Mary E. Ballestas, Etty N. Benveniste

Research output: Contribution to journalArticle

125 Scopus citations

Abstract

Intercellular adhesion molecule-1 (ICAM-1) is a cell surface glycoprotein which can be induced on astrocytes, the major glial cell of the central nervous system (CNS). In this study, we examined the effect of three proinflammatory cytokines, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interferon-gamma (IFN-γ), on the expression of ICAM-1 by primary rat astrocytes. Astrocytes constitutively express ICAM-1 mRNA and protein, which is enhanced by treatment with TNF-α, IL-1β and IFN-γ. TNF-α is the most potent inducer of ICAM-1 expression, followed by IL-1β, then IFN-γ. Kinetic analysis demonstrated optimum ICAM-1 mRNA expression after a 1-h exposure to TNF-α, 2 h exposure to IL-1β, and 4 h exposure to IFN-γ. Peak ICAM-1 protein expression was detected 12-16 h after treatment with TNF-α or IL-1β, and after a 24-h exposure to IFN-γ. Nuclear run-on analysis demonstrated that the ICAM-1 gene is transcribed under basal conditions in astrocytes, and that both TNF-α and IL-1β enhance transcriptional activation of the ICAM-1 gene. ICAM-1 mRNA stability studies determined that basal ICAM-1 mRNA has a half-life of about 1 h, and that TNF-α, IL-1β and IFN-γ have a modest effect on stabilization of basal ICAM-1 mRNA expression. These results indicate that under inflammatory conditions in the CNS, such as multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE), astrocytes can be induced to express the adhesion molecule ICAM-1, which can contribute to inflammatory events within the CNS.

Original languageEnglish (US)
Pages (from-to)209-220
Number of pages12
JournalJournal of neuroimmunology
Volume51
Issue number2
DOIs
StatePublished - May 1994

Keywords

  • Adhesion molecules
  • Central nervous system
  • Cytokines
  • Glial cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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