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    Deoxyribonuclease 1 reduces pathogenic effects of cigarette smoke exposure in the lung

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    Author
    King, PT; Sharma, R; O'Sullivan, KM; Callaghan, J; Dousha, L; Thomas, B; Ruwanpura, S; Lim, S; Farmer, MW; Jennings, BR; ...
    Date
    2017-09-21
    Source Title
    Scientific Reports
    Publisher
    NATURE PUBLISHING GROUP
    University of Melbourne Author/s
    Dousha, Lovisa; Anderson, Gary
    Affiliation
    Pharmacology and Therapeutics
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    King, P. T., Sharma, R., O'Sullivan, K. M., Callaghan, J., Dousha, L., Thomas, B., Ruwanpura, S., Lim, S., Farmer, M. W., Jennings, B. R., Finsterbusch, M., Brooks, G., Selemidis, S., Anderson, G. P., Holdsworth, S. R. & Bardin, P. G. (2017). Deoxyribonuclease 1 reduces pathogenic effects of cigarette smoke exposure in the lung. SCIENTIFIC REPORTS, 7 (1), https://doi.org/10.1038/s41598-017-12474-5.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/255179
    DOI
    10.1038/s41598-017-12474-5
    Abstract
    Our aim was to investigate if deoxyribonuclease (DNase) 1 is a potential therapeutic agent to reduce pathogenic effects of cigarette smoke exposure in the lung. Cigarette smoke causes protease imbalance with excess production of proteases, which is a key process in the pathogenesis of emphysema. The mechanisms responsible for this effect are not well-defined. Our studies demonstrate both in vitro and in vivo that cigarette smoke significantly increases the expression of neutrophil and macrophage extracellular traps with coexpression of the pathogenic proteases, neutrophil elastase and matrix metalloproteinases 9 and 12. This response to cigarette smoke was significantly reduced by the addition of DNase 1, which also significantly decreased macrophage numbers and lung proteolysis. DNase 1, a treatment currently in clinical use, can diminish the pathogenic effects of cigarette smoke.

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