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

54 Scopus citations

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    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.