DAMPs, endogenous danger signals fueling airway inflammation in COPD

    Research output: ThesisThesis fully internal (DIV)

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    Abstract

    COPD is a severe and progressive lung disease characterized by both chronic bronchitis as well as emphysema. In the Netherlands alone every year 7,000 people die from the consequences of COPD. COPD is caused by the chronic inhalation of toxic gases, like cigarette smoke. Furthermore, genetic predisposition contributes to the risk of developing COPD. To date, the underlying molecular and cellular mechanisms of COPD are largely unknown.
    In this thesis we studied the role of endogenous danger signals, called DAMPs, in COPD. We hypothesized that exposure of the lungs of genetically susceptible individuals to toxic gases induces immunogenic cell death followed by the release of DAMPs which contribute the airway inflammation in COPD patients. Here, we used both in vitro cellular models with cells isolated from COPD patients and controls as well as in vivo mouse models to show that airway epithelial cells release DAMPs upon cigarette smoke exposure and that these DAMPs have pro-inflammatory functions. Moreover, we showed that the release of specific DAMPs is increased in COPD patients. Furthermore, we have identified several novel susceptibility genes for cigarette smoke-induced airway inflammation and DAMP release. These results indicate that DAMPs play an important role in the pathophysiology of COPD.
    In conclusion, this thesis shows that DAMPs are a novel possible target for future therapies of COPD patients. Future studies are needed to investigate which DAMPs or DAMP receptors show the highest therapeutic potential upon inhibition.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Heijink, Irene, Supervisor
    • van Oosterhout, Antoon, Supervisor
    • Nawijn, Martijn, Co-supervisor
    • Brusselle, Guy, Assessment committee, External person
    • Krysko, D. V., Assessment committee, External person
    • Heeringa, Peter, Assessment committee
    Award date10-May-2017
    Place of Publication[Groningen]
    Publisher
    Print ISBNs978-90-367-9766-5
    Electronic ISBNs978-90-367-9765-8
    Publication statusPublished - 2017

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