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Transforming growth factor–beta inhibition of cytokine‐induced vascular cell adhesion molecule‐1 expression in human astrocytes
Author(s) -
Winkler Margaret K.,
Benveniste Etty N.
Publication year - 1998
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/(sici)1098-1136(199802)22:2<171::aid-glia8>3.0.co;2-a
Subject(s) - proinflammatory cytokine , biology , cytokine , cell adhesion molecule , vcam 1 , microbiology and biotechnology , tumor necrosis factor alpha , immunology , cell adhesion , inflammation , transforming growth factor beta , signal transduction , cell , icam 1 , genetics
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‐β, 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‐α, IL‐1β, IFN‐γ) in the absence or presence of TGF‐β. 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‐α and IL‐1β. The inclusion of TGF‐β1 or TGF‐β2 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‐β is an important regulator of cytokine induced VCAM‐1 expression on astrocytes and may prove useful clinically in controlling CNS inflammation. GLIA 22:171–179, 1998. © 1998 Wiley‐Liss, Inc.