title: Transforming growth factor-beta inhibition of cytokine-induced vascular cell adhesion molecule-1 expression in human astrocytes.
abstract: Leukocyte transmigration across the blood-brain barrier (BBB) is a cardinal feature of central nervous system (CNS) inflammation. Astrocytes form an integral part, both structurally and functionally, of the BBB. Vascular cell adhesion molecule-1 (VCAM-1), a member of the immunoglobulin gene superfamily, is involved in extravasation into inflamed tissues and activation of T-lymphocytes. In this study, we investigated the role of TGF-beta, an immunosuppressive cytokine, in regulating cytokine-induced VCAM-1 expression in astrocytes. Human astroglioma cell lines and primary human fetal astrocytes were examined for VCAM-1 gene expression after treatment with proinflammatory cytokines (TNF-alpha, IL-1beta, IFN-gamma) in the absence or presence of TGF-beta. Astroglioma cell lines as well as primary human fetal astrocytes expressed low levels of VCAM-1 constitutively, and the proinflammatory cytokines induced marked increases in VCAM-1 expression, particularly TNF-alpha and IL-1beta. The inclusion of TGF-beta1 or TGF-beta2 with the proinflammatory cytokines inhibited VCAM-1 gene expression to varying degrees (33-93%) in all the astroglioma cell lines and primary fetal cells. These results indicate that TGF-beta is an important regulator of cytokine induced VCAM-1 expression on astrocytes and may prove useful clinically in controlling CNS inflammation.
authors.affiliation: Department of Cell Biology, the University of Alabama at Birmingham, 35294-0005, USA.
authors.forename: M K
authors.initials: MK
authors.lastname: Winkler
authors.forename: E N
authors.initials: EN
authors.lastname: Beveniste
mesh_terms: D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005434:Flow Cytometry; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D015347:RNA Probes; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D012260:Ribonucleases / Q000378:metabolism; D013379:Substrate Specificity; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
chemical_list: D016207:Cytokines; D015347:RNA Probes; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D019010:Vascular Cell Adhesion Molecule-1; D012260:Ribonucleases