The Journal of Immunology, Vol 157, Issue 2 892-900, Copyright © 1996 by American Association of Immunologists

ARTICLES

Stimulus-specific inhibition of intracellular adhesion molecule-1 gene expression by TGF-beta

P Shrikant, SJ Lee, I Kalvakolanu, RM Ransohoff and EN Benveniste
Department of Cell Biology, University of Alabama at Birmingham 35294, USA.

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- beta, an immunosuppressive cytokine, in regulating ICAM-1 expression in glial cells. We previously demonstrated that TNF-alpha, IL-1 beta, IFN- gamma, or IFN-gamma plus LPS (IFN-gamma/LPS) can enhance ICAM-1 expression in astrocytes, while microglia express ICAM-1 only in response to IFN-gamma or IFN-gamma/LPS. TGF-beta alone has a minimal effect on constitutive ICAM-1 expression in either astrocytes or microglia, but inhibits, in a time-dependent manner, TNF-alpha- or IL-1 beta-induced ICAM-1 mRNA and protein expression in astrocytes. Interestingly, TGF-beta has no effect on IFN-gamma- or IFN-gamma/LPS- induced ICAM-1 expression in astrocytes or microglia. Inhibition of TNF- alpha- or IL-1 beta-induced ICAM-1 mRNA levels by TGF-beta 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- beta inhibited TNF-alpha- and IL-1 beta-induced ICAM-1 expression, but IFN-gamma induction of ICAM-1 was unaffected. These results indicate that TGF-beta suppresses ICAM-1 expression in glial cells in a stimulus- specific manner.

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