• Login as Editor
    View Item 
    •   Yeshiva Academic Institutional Repository
    • Albert Einstein College of Medicine (AECOM)
    • Albert Einstein College of Medicine: Doctoral Dissertations
    • View Item
    •   Yeshiva Academic Institutional Repository
    • Albert Einstein College of Medicine (AECOM)
    • Albert Einstein College of Medicine: Doctoral Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Regulation of inflammation in the central nervous system by interleukin-1 and transforming growth factor-beta-1

    Thumbnail

    Date
    1996
    Author
    Cuff, Carolyn Ann
    Metadata
    Show full item record
    Share
    Abstract
    Inflammation within the central nervous system (CNS) results in significant pathology and is controlled by properties of the blood-brain-barrier (BBB). We developed an animal model of retinal inflammation in the rabbit using the proinflammatory cytokine IL-1beta to examine mechanisms involved in regulation of CNS inflammation. Intra-vitreal injection of 300 U IL-1 induced inflammation of the epiretinal vessels, that form a blood-retina barrier similar to the BBB, characterized by hemorrhage, leukocyte infiltration, and an increase in vascular permeability. To test the hypothesis that the perivascular macrophage plays a role in maintaining the BBB, we studied the activation state of this cell during the course of inflammation by examining its morphology and expression of surface antigens. We found that IL-1 caused activation of these cells beginning 3 h post-IL-1 injection. Because monocytes constitute a major part of the inflammatory infiltrate, we examined the contribution of macrophage chemotactic factors towards CNS inflammation by in situ hybridization for monocyte chemotactic protein-1 (MCP-1). MCP-1 message was detected in perivasular cells by 2 h following IL-1 treatment. At later time-points, message was also detected in astrocytes and endothelial cells. We then determined the effect of the immunosuppressive cytokine transforming growth factor-beta1 (TGF-beta). TGF-beta significantly reduced IL-1-induced cellular inflammation and hemorrhage, but did not affect edema. Injection of TGF-beta alone increased leakage of serum proteins, suggesting that the effects of TGF-beta on CNS inflammation are complex. Endothelial cell cultures were utilized to examine further the mechanism of TGF-{dollar}\beta{dollar}-mediated immune suppression. TGF-beta decreased TNF-alpha-induced expression of the adhesion molecules E-selectin and IG9 but did not decrease induced expression of VCAM-1 and ICAM-1. TGF-{dollar}\beta{dollar} treatment also reduced TNF-induced expression of IL-8 protein and message but had no significant effect on TNF-induced MCP-1 protein expression. However, TGF-{dollar}\beta{dollar} significantly decreased TNF-induced MCP-1 mRNA. These results indicate that the mechanism of TGF-{dollar}\beta{dollar} mediated immunosuppression may be mediated through reduction in adhesion molecule and chemokine production by endothelial cells. The identification of specific mediators and regulators of CNS inflammation in these studies may contribute towards our understanding the mechanisms in the pathogenesis of inflammatory disorders and lead to strategies for intervention.
    Permanent Link(s)
    https://ezproxy.yu.edu/login?url=http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:9615566
    https://hdl.handle.net/20.500.12202/3644
    Citation
    Source: Dissertation Abstracts International, Volume: 57-01, Section: B, page: 2240.
    *This is constructed from limited available data and may be imprecise.
    Collections
    • Albert Einstein College of Medicine: Doctoral Dissertations [1673]

    Yeshiva University Libraries copyright © 2021  DuraSpace
    YAIR Self-Deposit | YAIR User's Guide | Take Down Policy | Contact Us
    Yeshiva University
     

     

    Browse

    AllCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

    My Account

    Login as Editor

    Statistics

    View Usage Statistics

    Yeshiva University Libraries copyright © 2021  DuraSpace
    YAIR Self-Deposit | YAIR User's Guide | Take Down Policy | Contact Us
    Yeshiva University