Stimulus-specific inhibition of intracellular adhesion molecule-1 gene expression by TGF-beta.
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.
Shrikant
P
P
Department of Cell Biology, University of Alabama at Birmingham 35294, USA.
Lee
S J
SJ
Kalvakolanu
I
I
Ransohoff
R M
RM
Benveniste
E N
EN
D001254:Astrocytoma / Q000235:genetics; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D004355:Drug Stability; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000235:genetics*; D017628:Microglia / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1