• About
    • Login
    View Item 
    •   Institutional Repository Home
    • Electronic Theses and Dissertations
    • Electronic Theses and Dissertations
    • View Item
    •   Institutional Repository Home
    • Electronic Theses and Dissertations
    • Electronic Theses and Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of Institutional RepositoryCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsDepartmentThis CollectionBy Issue DateAuthorsTitlesSubjectsDepartment

    My Account

    LoginRegister

    Mechanisms Regulating Macrophage Activation and Function during Bacterial Infection and Carcinogenesis

    Hardbower, Dana Michelle
    : https://etd.library.vanderbilt.edu/etd-03142017-111446
    http://hdl.handle.net/1803/10774
    : 2017-03-21

    Abstract

    Macrophages represent a dynamic and plastic subset of the innate immune system. Macrophage functions include immune surveillance and clearance of pathogens, but they have also been implicated in tumorigenesis. Macrophage activation along the M1 (classical, pro-inflammatory macrophage) to M2 (alternatively activated macrophage) axis is a tightly regulated process. Some pathways that regulate macrophage activation are known, but many uncertainties remain. To address questions related to macrophage activation, we chose the highly prolific human pathogen, Helicobacter pylori. H. pylori infection leads to chronic gastric inflammation and macrophages are an essential component of H. pylori-mediated gastritis. The studies outlined in this dissertation have identified two different proteins that regulate macrophage activation. Epidermal growth factor receptor (EGFR) signaling is an essential component of macrophage activation along both M1 and M2 paradigms. Deletion of Egfr in macrophages results in protection from H. pylori-mediated gastritis due to decreased pro-inflammatory M1 activation. Additionally, loss of EGFR signaling in macrophages protected mice from colitis-associated carcinogenesis, due to decreased M1 and M2 activation, and decreased angiogenesis. Conversely, ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine metabolism, serves to promote immune tolerance within the gastric niche. Loss of ODC in macrophages led to increased M1 macrophage activation and increased pro-inflammatory cytokine production. The enhanced M1 macrophage activation was due to alterations in histone modifications to promote transcription. Overall, this dissertation demonstrates that increased knowledge regarding the regulation of macrophage activation can improve our understanding of macrophage biology in inflammation-mediated diseases.
    Show full item record

    Files in this item

    Icon
    Name:
    Hardbower.pdf
    Size:
    75.84Mb
    Format:
    PDF
    View/Open

    This item appears in the following collection(s):

    • Electronic Theses and Dissertations

    Connect with Vanderbilt Libraries

    Your Vanderbilt

    • Alumni
    • Current Students
    • Faculty & Staff
    • International Students
    • Media
    • Parents & Family
    • Prospective Students
    • Researchers
    • Sports Fans
    • Visitors & Neighbors

    Support the Jean and Alexander Heard Libraries

    Support the Library...Give Now

    Gifts to the Libraries support the learning and research needs of the entire Vanderbilt community. Learn more about giving to the Libraries.

    Become a Friend of the Libraries

    Quick Links

    • Hours
    • About
    • Employment
    • Staff Directory
    • Accessibility Services
    • Contact
    • Vanderbilt Home
    • Privacy Policy