Cigarette smoke exposure alters phosphodiesterases in human structural lung cells
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Cigarette smoke exposure alters phosphodiesterases in human structural lung cells. / Zuo, Haoxiao; Faiz, Alen; van den Berge, Maarten; Mudiyanselage, Senani N H Rathnayake; Borghuis, Theo; Timens, Wim; Nikolaev, Viacheslav O; Burgess, Janette K; Schmidt, Martina.
In: AM J PHYSIOL-LUNG C, Vol. 318, No. 1, 01.01.2020, p. L59-L64.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Cigarette smoke exposure alters phosphodiesterases in human structural lung cells
AU - Zuo, Haoxiao
AU - Faiz, Alen
AU - van den Berge, Maarten
AU - Mudiyanselage, Senani N H Rathnayake
AU - Borghuis, Theo
AU - Timens, Wim
AU - Nikolaev, Viacheslav O
AU - Burgess, Janette K
AU - Schmidt, Martina
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
U2 - 10.1152/ajplung.00319.2019
DO - 10.1152/ajplung.00319.2019
M3 - SCORING: Journal article
C2 - 31664853
VL - 318
SP - L59-L64
IS - 1
ER -
