Stimulus-specific inhibition of intercellular adhesion molecule-1 gene expression by TGF-β

Protul Shrikant, Sung Joong Lee, Indira Kalvakolanu, Richard M. Ransohoff, Etty N. Benveniste

Research output: Contribution to journalArticle

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Abstract

Astrocytes and microglia, the two major glial cells within the central nervous system, can function as immune effector cells upon activation. Intercellular adhesion molecule-1 (ICAM-1), a cell surface glycoprotein involved in extravasation into inflamed tissue and Ag-specific activation of T lymphocytes, can be induced in astrocytes and microglia by numerous stimuli. In this study, we investigated the role of TGF-β, an immunosuppressive cytokine, in regulating ICAM-1 expression in glial cells. We previously demonstrated that TNF-α, IL-1β, IFN-γ, or IFN-γ plus LPS (IFN-γ/LPS) can enhance ICAM-1 expression in astrocytes, while microglia express ICAM-1 only in response to IFN-γ or IFN-γ/LPS. TGF-β alone has a minimal effect on constitutive ICAM-1 expression in either astrocytes or microglia, but inhibits, in a time-dependent manner, TNF-α- or IL-1β- induced ICAM-1 mRNA and protein expression in astrocytes. Interestingly, TGF- β has no effect on IFN-γ- or IFN-γ/LPS-induced ICAM-1 expression in astrocytes or microglia. Inhibition of TNF-α- or IL-1β-induced ICAM-1 mRNA levels by TGF-β in astrocytes was not due to degradation of ICAM-1 message, rather, inhibition was mediated at the transcriptional level. Similar results were observed in two human astroglioma cell lines, CRT and STT; TGF-β inhibited TNF-α- and IL-1β-induced ICAM-1 expression, but IFN-γ induction of ICAM-1 was unaffected. These results indicate that TGF-β suppresses ICAM- 1 expression in glial cells in a stimulus-specific manner.

Original languageEnglish (US)
Pages (from-to)892-900
Number of pages9
JournalJournal of Immunology
Volume157
Issue number2
StatePublished - Jul 15 1996
Externally publishedYes

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Intercellular Adhesion Molecule-1
Gene Expression
Astrocytes
Microglia
Interleukin-1
Neuroglia
Messenger RNA
Membrane Glycoproteins
Astrocytoma
Immunosuppressive Agents
Central Nervous System
Cytokines
T-Lymphocytes
Cell Line

ASJC Scopus subject areas

  • Immunology

Cite this

Shrikant, P., Lee, S. J., Kalvakolanu, I., Ransohoff, R. M., & Benveniste, E. N. (1996). Stimulus-specific inhibition of intercellular adhesion molecule-1 gene expression by TGF-β. Journal of Immunology, 157(2), 892-900.

Stimulus-specific inhibition of intercellular adhesion molecule-1 gene expression by TGF-β. / Shrikant, Protul; Lee, Sung Joong; Kalvakolanu, Indira; Ransohoff, Richard M.; Benveniste, Etty N.

In: Journal of Immunology, Vol. 157, No. 2, 15.07.1996, p. 892-900.

Research output: Contribution to journalArticle

Shrikant, P, Lee, SJ, Kalvakolanu, I, Ransohoff, RM & Benveniste, EN 1996, 'Stimulus-specific inhibition of intercellular adhesion molecule-1 gene expression by TGF-β', Journal of Immunology, vol. 157, no. 2, pp. 892-900.
Shrikant P, Lee SJ, Kalvakolanu I, Ransohoff RM, Benveniste EN. Stimulus-specific inhibition of intercellular adhesion molecule-1 gene expression by TGF-β. Journal of Immunology. 1996 Jul 15;157(2):892-900.
Shrikant, Protul ; Lee, Sung Joong ; Kalvakolanu, Indira ; Ransohoff, Richard M. ; Benveniste, Etty N. / Stimulus-specific inhibition of intercellular adhesion molecule-1 gene expression by TGF-β. In: Journal of Immunology. 1996 ; Vol. 157, No. 2. pp. 892-900.
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