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 journalArticlepeer-review

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

Fingerprint Dive into the research topics of 'Stimulus-specific inhibition of intercellular adhesion molecule-1 gene expression by TGF-β'. Together they form a unique fingerprint.

Cite this