• Login
    View Item 
    •   Home
    • Brock Theses
    • Masters Theses
    • M.Sc. Applied Health Sciences
    • View Item
    •   Home
    • Brock Theses
    • Masters Theses
    • M.Sc. Applied Health Sciences
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of BrockUCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjectsProfilesView

    My Account

    LoginRegister

    Statistics

    Display statistics

    Inhibition of allergen-mediated mast cell activation by TAK1 inhibitor 5Z-7-oxozeaenol

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Brock_Watson_Colton_2017.pdf
    Size:
    4.586Mb
    Format:
    PDF
    Download
    Author
    Watson, Colton JF
    Keyword
    Allergy
    Mast Cell
    5Z-7-oxozeaenol
    Transforming growth factor-beta-activated kinase 1 (TAK1)
    Inflammation
    
    Metadata
    Show full item record
    URI
    http://hdl.handle.net/10464/12992
    Abstract
    Introduction & Aim: Allergic inflammatory disorders are at epidemic levels worldwide. Mast cells drive this inappropriate immune response via release of a variety of pro-inflammatory mediators in response to environmental cues detected by the IgE-FcεRI complex, but we do not fully understand the contributing molecular mechanisms. Transforming growth factor β-activated kinase 1 (TAK1) is a known participant in related signaling through MAPK and NF-κB; however the role of TAK1 in IgE-FcεRI signaling and resultant allergic inflammation remains unknown. We aim to assess the role of TAK1 in IgE-mediated mast cell activation. Methods: Bone marrow-derived mast cells were sensitized with allergen-specific IgE and treated with the corresponding allergen for various times in the presence or absence of 5Z-7-oxozeaenol. Mast cell signaling was measured by western blotting, induced gene expression by qPCR, pro-inflammatory mediator release by ELISA and mast cell degranulation by β-hexosaminidase release assay. Results: TAK1-inhibition resulted in significant impairment in the phosphorylation of various MAPKs (p38, ERK and JNK) as well as NF-κB pathway kinase IκBα. Impaired gene expression of pro-inflammatory cytokines IL-4, IL-6, IL-13, and chemokines CCL1, -2, and -3 were detected. Furthermore, a drastic decrease in the concentration of pro-inflammatory cytokines, IL-6 and TNF, and chemokines CCL1 and CCL2, in stimulated cell supernatants was detected. Finally, a significant inhibition of mast cell degranulation was also observed in the TAK1-inhibited cells. Conclusion and Significance: These results suggest that TAK1 acts as a signaling node linking the MAPK and NF-κB pathways in mast cells responding to allergen and may warrant consideration in future therapeutic development.
    Collections
    M.Sc. Applied Health Sciences

    entitlement

     
    DSpace software (copyright © 2002 - 2022)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.