The role of epithelial-fibroblast communication in asthma and COPD

Emmanuel Osei

    Research output: ThesisThesis fully internal (DIV)

    1134 Downloads (Pure)

    Abstract

    Asthma and COPD are chronic lung diseases that have no cure. Both diseases involve inflammation and scarring of the airways, resulting in airway wall fibrosis and airway narrowing. Airways are covered with epithelium, important in immune defense and closely collaborating with underlying cells like fibroblasts. Fibroblasts are cells that produce connective tissue proteins and regulate its normal structure. Our hypothesis is that a disturbed collaboration and interaction between epithelial cells and fibroblasts leads to changes in normal regulation of inflammation, formation and structure of connective tissue, contributing to the disease mechanism in COPD and asthma. In this thesis, we developed a cell culture model to study lung epithelial and fibroblast communication. We found that the release of an inflammatory mediator, interleukin-1α (IL-1α) is very important in epithelial regulation of fibroblast functions. Further, when we exposed airway epithelial cells to cigarette smoke, the major risk factor for COPD, this caused more release of IL-1α which subsequently caused lung fibroblasts to release higher levels of other inflammatory mediators. We also found that fibroblasts from COPD patients have lower levels of the master regulatory molecule, miRNA-146a-5p, that normally controls excessive IL-1 signaling. Also we also found more release of IL-1α from asthmatic-derived airway epithelial cells and that IL-1 causes asthmatic-derived fibroblasts to form disorganized of collagen, a connective tissue protein essential for normal tissue repair.
    Our work sheds new light on how abnormal epithelial-fibroblast communication contributes to the disease process of asthma and COPD and opens new avenues for therapeutic research.
    Translated title of the contributionDe rol van epithelieel-fibroblast communicatie in astma en COPD
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Timens, Wim, Supervisor
    • Hackett, Tillie, Supervisor
    • Heijink, Irene, Supervisor
    • Brandsma, Corry-Anke, Co-supervisor
    Award date6-Sep-2017
    Edition[Groningen]
    Publisher
    Print ISBNs978-90-367-9978-2
    Electronic ISBNs978-90-367-9977-5
    Publication statusPublished - 2017

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