Influenza A virus infection and cigarette smoke impair bronchodilator responsiveness to β-adrenoceptor agonists in mouse lung.

Donovan, C; Seow, HJ; Bourke, JE; Vlahos, R

Influenza A virus infection and cigarette smoke impair bronchodilator responsiveness to β-adrenoceptor agonists in mouse lung.

Donovan, C

Seow, HJ Bourke, JE Vlahos, R

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Publisher:: Portland Press Ltd.
Publication Type:: Journal Article
Citation:: Clin Sci (Lond), 2016, 130, (10), pp. 829-837
Issue Date:: 2016-05-01

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Field	Value	Language
dc.contributor.author	Donovan, C https://orcid.org/0000-0003-4558-329X
dc.contributor.author	Seow, HJ
dc.contributor.author	Bourke, JE
dc.contributor.author	Vlahos, R
dc.date.accessioned	2022-08-11T06:28:49Z
dc.date.available	2016-02-23
dc.date.available	2022-08-11T06:28:49Z
dc.date.issued	2016-05-01
dc.identifier.citation	Clin Sci (Lond), 2016, 130, (10), pp. 829-837
dc.identifier.issn	0143-5221
dc.identifier.issn	1470-8736
dc.identifier.uri	http://hdl.handle.net/10453/159948
dc.description.abstract	β2-adrenoceptor agonists are the mainstay therapy for patients with asthma but their effectiveness in cigarette smoke (CS)-induced lung disease such as chronic obstructive pulmonary disease (COPD) is limited. In addition, bronchodilator efficacy of β2-adrenoceptor agonists is decreased during acute exacerbations of COPD (AECOPD), caused by respiratory viruses including influenza A. Therefore, the aim of the present study was to assess the effects of the β2-adrenoceptor agonist salbutamol (SALB) on small airway reactivity using mouse precision cut lung slices (PCLS) prepared from CS-exposed mice and from CS-exposed mice treated with influenza A virus (Mem71, H3N1). CS exposure alone reduced SALB potency and efficacy associated with decreased β2-adrenoceptor mRNA expression, and increased tumour necrosis factor α (TNFα) and interleukin-1β (IL-1β) expression. This impaired relaxation was restored by day 12 in the absence of further CS exposure. In PCLS prepared after Mem71 infection alone, responses to SALB were transient and were not well maintained. CS exposure prior to Mem71 infection almost completely abolished relaxation, although β2-adrenoceptor and TNFα and IL-1β expression were unaltered. The present study has shown decreased sensitivity to SALB after CS or a combination of CS and Mem71 occurs by different mechanisms. In addition, the PCLS technique and our models of CS and influenza infection provide a novel setting for assessment of alternative bronchodilators.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	Portland Press Ltd.
dc.relation.ispartof	Clin Sci (Lond)
dc.relation.isbasedon	10.1042/CS20160093
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	11 Medical and Health Sciences
dc.subject.classification	Cardiovascular System & Hematology
dc.subject.mesh	Adrenergic beta-Agonists
dc.subject.mesh	Animals
dc.subject.mesh	Bronchodilator Agents
dc.subject.mesh	Influenza A virus
dc.subject.mesh	Lung
dc.subject.mesh	Male
dc.subject.mesh	Mice
dc.subject.mesh	Pulmonary Disease, Chronic Obstructive
dc.subject.mesh	Receptors, Adrenergic
dc.subject.mesh	Smoking
dc.subject.mesh	Tobacco
dc.subject.mesh	Tumor Necrosis Factor-alpha
dc.subject.mesh	Lung
dc.subject.mesh	Animals
dc.subject.mesh	Mice
dc.subject.mesh	Influenza A virus
dc.subject.mesh	Tobacco
dc.subject.mesh	Pulmonary Disease, Chronic Obstructive
dc.subject.mesh	Tumor Necrosis Factor-alpha
dc.subject.mesh	Receptors, Adrenergic
dc.subject.mesh	Adrenergic beta-Agonists
dc.subject.mesh	Bronchodilator Agents
dc.subject.mesh	Smoking
dc.subject.mesh	Male
dc.title	Influenza A virus infection and cigarette smoke impair bronchodilator responsiveness to β-adrenoceptor agonists in mouse lung.
dc.type	Journal Article
utslib.citation.volume	130
utslib.location.activity	England
utslib.for	11 Medical and Health Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
utslib.copyright.status	open_access	*
dc.date.updated	2022-08-11T06:28:48Z
pubs.issue	10
pubs.publication-status	Published
pubs.volume	130
utslib.citation.issue	10

Abstract:

β2-adrenoceptor agonists are the mainstay therapy for patients with asthma but their effectiveness in cigarette smoke (CS)-induced lung disease such as chronic obstructive pulmonary disease (COPD) is limited. In addition, bronchodilator efficacy of β2-adrenoceptor agonists is decreased during acute exacerbations of COPD (AECOPD), caused by respiratory viruses including influenza A. Therefore, the aim of the present study was to assess the effects of the β2-adrenoceptor agonist salbutamol (SALB) on small airway reactivity using mouse precision cut lung slices (PCLS) prepared from CS-exposed mice and from CS-exposed mice treated with influenza A virus (Mem71, H3N1). CS exposure alone reduced SALB potency and efficacy associated with decreased β2-adrenoceptor mRNA expression, and increased tumour necrosis factor α (TNFα) and interleukin-1β (IL-1β) expression. This impaired relaxation was restored by day 12 in the absence of further CS exposure. In PCLS prepared after Mem71 infection alone, responses to SALB were transient and were not well maintained. CS exposure prior to Mem71 infection almost completely abolished relaxation, although β2-adrenoceptor and TNFα and IL-1β expression were unaltered. The present study has shown decreased sensitivity to SALB after CS or a combination of CS and Mem71 occurs by different mechanisms. In addition, the PCLS technique and our models of CS and influenza infection provide a novel setting for assessment of alternative bronchodilators.

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http://hdl.handle.net/10453/159948