Cigarette Smoke exposure Alters Phosphodiesterases in Human Structural Lung Cells.

Zuo, H; Faiz, A; van den Berge, M; Mudiyanselage, SNHR; Borghuis, T; Timens, W; Nikolaev, VO; Burgess, JK; Schmidt, M

Cigarette Smoke exposure Alters Phosphodiesterases in Human Structural Lung Cells.

Zuo, H Faiz, A

van den Berge, M Mudiyanselage, SNHR Borghuis, T Timens, W Nikolaev, VO Burgess, JK Schmidt, M

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Publisher:: American Physiological Society
Publication Type:: Journal Article
Citation:: American Journal of Physiology: Lung Cellular and Molecular Physiology, 2020, 318, (1), pp. 59-64
Issue Date:: 2020

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Field	Value	Language
dc.contributor.author	Zuo, H
dc.contributor.author	Faiz, A https://orcid.org/0000-0003-1740-3538
dc.contributor.author	van den Berge, M
dc.contributor.author	Mudiyanselage, SNHR
dc.contributor.author	Borghuis, T
dc.contributor.author	Timens, W
dc.contributor.author	Nikolaev, VO
dc.contributor.author	Burgess, JK
dc.contributor.author	Schmidt, M
dc.date.accessioned	2020-11-08T18:48:01Z
dc.date.available	2020-11-08T18:48:01Z
dc.date.issued	2020
dc.identifier.citation	American Journal of Physiology: Lung Cellular and Molecular Physiology, 2020, 318, (1), pp. 59-64
dc.identifier.issn	1040-0605
dc.identifier.issn	1522-1504
dc.identifier.uri	http://hdl.handle.net/10453/143847
dc.description.abstract	Cigarette smoke (CS), a highly complex mixture containing more than 4000 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 (COPD) with chronic bronchitis and a history of frequent exacerbations. Additional selective PDE inhibitors are being tested in pre-clinical 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.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	American Physiological Society
dc.relation.ispartof	American Journal of Physiology: Lung Cellular and Molecular Physiology
dc.relation.isbasedon	10.1152/ajplung.00319.2019
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.subject	0606 Physiology, 1116 Medical Physiology
dc.subject.classification	Respiratory System
dc.subject.mesh	Lung
dc.subject.mesh	Humans
dc.subject.mesh	Pulmonary Disease, Chronic Obstructive
dc.subject.mesh	Benzamides
dc.subject.mesh	Aminopyridines
dc.subject.mesh	Cyclopropanes
dc.subject.mesh	Phosphoric Diester Hydrolases
dc.subject.mesh	RNA, Messenger
dc.subject.mesh	Smoking
dc.subject.mesh	Smoke
dc.subject.mesh	Gene Expression
dc.subject.mesh	Adult
dc.subject.mesh	Middle Aged
dc.subject.mesh	Female
dc.subject.mesh	Male
dc.subject.mesh	Phosphodiesterase 4 Inhibitors
dc.subject.mesh	Tobacco Products
dc.subject.mesh	Adult
dc.subject.mesh	Aminopyridines
dc.subject.mesh	Benzamides
dc.subject.mesh	Cyclopropanes
dc.subject.mesh	Female
dc.subject.mesh	Gene Expression
dc.subject.mesh	Humans
dc.subject.mesh	Lung
dc.subject.mesh	Male
dc.subject.mesh	Middle Aged
dc.subject.mesh	Phosphodiesterase 4 Inhibitors
dc.subject.mesh	Phosphoric Diester Hydrolases
dc.subject.mesh	Pulmonary Disease, Chronic Obstructive
dc.subject.mesh	RNA, Messenger
dc.subject.mesh	Smoke
dc.subject.mesh	Smoking
dc.subject.mesh	Tobacco Products
dc.title	Cigarette Smoke exposure Alters Phosphodiesterases in Human Structural Lung Cells.
dc.type	Journal Article
utslib.citation.volume	318
utslib.location.activity	United States
utslib.for	0606 Physiology
utslib.for	1116 Medical Physiology
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access	*
pubs.consider-herdc	false
dc.date.updated	2020-11-08T18:47:57Z
pubs.issue	1
pubs.publication-status	Published
pubs.volume	318
utslib.citation.issue	1

Abstract:

Cigarette smoke (CS), a highly complex mixture containing more than 4000 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 (COPD) with chronic bronchitis and a history of frequent exacerbations. Additional selective PDE inhibitors are being tested in pre-clinical 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.

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http://hdl.handle.net/10453/143847