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Updated: Aug 9, 2026

Analysis of Schwann-astrocyte Interactions Using In Vitro Assays
Published on: January 14, 2011
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.
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-alpha), interleukin-1 beta (IL-1 beta), and interferon-gamma (IFN-gamma), 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-alpha, IL-1 beta and IFN-gamma. TNF-alpha is the most potent inducer of ICAM-1 expression, followed by IL-1 beta, then IFN-gamma. Kinetic analysis demonstrated optimum ICAM-1 mRNA expression after a 1-h exposure to TNF-alpha, 2 h exposure to IL-1 beta, and 4 h exposure to IFN-gamma. Peak ICAM-1 protein expression was detected 12-16 h after treatment with TNF-alpha or IL-1 beta, and after a 24-h exposure to IFN-gamma. Nuclear run-on analysis demonstrated that the ICAM-1 gene is transcribed under basal conditions in astrocytes, and that both TNF-alpha and IL-1 beta 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-alpha, IL-1 beta and IFN-gamma 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.
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