Publication

Cigarette smoke exposure alters phosphodiesterases in human structural lung cells

Zuo, H., Faiz, A., van den Berge, M., Mudiyanselage, S. N. H. R., Borghuis, T., Timens, W., Nikolaev, V. O., Burgess, J. K. & Schmidt, M., Jan-2020, In : American Journal of Physiology - Lung Cellular and Molecular Physiology. 318, 1, p. L59-L64 6 p.

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Documents

  • Cigarette Smoke exposure Alters Phosphodiesterases in Human Structural Lung Cells

    Final author's version, 590 KB, PDF document

    Embargo ends: 30/10/2020

  • Cigarette smoke exposure alters phosphodiesterases in human structural lung cells

    Final publisher's version, 793 KB, PDF document

DOI

Cigarette smoke (CS), a highly complex mixture containing more than 4,000 compounds, causes aberrant cell responses leading to tissue damage around the airways and alveoli, which underlies various lung diseases. Phosphodiesterases (PDEs) are a family of enzymes that hydrolyze cyclic nucleotides. PDE inhibition induces bronchodilation, reduces the activation and recruitment of inflammatory cells, and the release of various cytokines. Currently, the selective PDE4 inhibitor roflumilast is an approved add-on treatment for patients with severe chronic obstructive pulmonary disease with chronic bronchitis and a history of frequent exacerbations. Additional selective PDE inhibitors are being tested in preclinical and clinical studies. However, the effect of chronic CS exposure on the expression of PDEs is unknown. Using mRNA isolated from nasal and bronchial brushes and lung tissues of never smokers and current smokers, we compared the gene expression of 25 PDE coding genes. Additionally, the expression and distribution of PDE3A and PDE4D in human lung tissues was examined. This study reveals that chronic CS exposure modulates the expression of various PDE members. Thus, CS exposure may change the levels of intracellular cyclic nucleotides and thereby impact the efficiency of PDE-targeted therapies.

Original languageEnglish
Pages (from-to)L59-L64
Number of pages6
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume318
Issue number1
Early online date30-Oct-2019
Publication statusPublished - Jan-2020

    Keywords

  • cAMP, cigarette smoke, phosphodiesterase, ROFLUMILAST N-OXIDE, INHIBITORS, EMPHYSEMA, CGMP

ID: 100700410