PMID- 27128803 OWN - NLM STAT- MEDLINE DCOM- 20170414 LR - 20231213 IS - 1470-8736 (Electronic) IS - 0143-5221 (Print) IS - 0143-5221 (Linking) VI - 130 IP - 10 DP - 2016 May 1 TI - Influenza A virus infection and cigarette smoke impair bronchodilator responsiveness to beta-adrenoceptor agonists in mouse lung. PG - 829-37 LID - 10.1042/CS20160093 [doi] AB - beta2-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 beta2-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 beta2-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 beta2-adrenoceptor mRNA expression, and increased tumour necrosis factor alpha (TNFalpha) and interleukin-1beta (IL-1beta) 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 beta2-adrenoceptor and TNFalpha and IL-1beta 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. CI - (c) 2016 The Author(s). FAU - Donovan, Chantal AU - Donovan C AD - Biomedicine Discovery Institute, Department of Pharmacology, Monash University, Clayton, Victoria 3800, Australia Lung Health Research Centre, Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria 3010, Australia. FAU - Seow, Huei Jiunn AU - Seow HJ AD - Lung Health Research Centre, Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria 3010, Australia School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria 3083, Australia. FAU - Bourke, Jane E AU - Bourke JE AD - Biomedicine Discovery Institute, Department of Pharmacology, Monash University, Clayton, Victoria 3800, Australia Lung Health Research Centre, Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria 3010, Australia. FAU - Vlahos, Ross AU - Vlahos R AD - Lung Health Research Centre, Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria 3010, Australia School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria 3083, Australia ross.vlahos@rmit.edu.au. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160410 PL - England TA - Clin Sci (Lond) JT - Clinical science (London, England : 1979) JID - 7905731 RN - 0 (Adrenergic beta-Agonists) RN - 0 (Bronchodilator Agents) RN - 0 (Receptors, Adrenergic) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM CIN - Clin Sci (Lond). 2016 May 1;130(10):839-41. PMID: 27128804 MH - Adrenergic beta-Agonists/*pharmacology MH - Animals MH - Bronchodilator Agents/*therapeutic use MH - *Influenza A virus MH - Lung/metabolism/*virology MH - Male MH - Mice MH - Pulmonary Disease, Chronic Obstructive/drug therapy/metabolism MH - Receptors, Adrenergic/metabolism MH - Smoking/*adverse effects MH - Nicotiana/adverse effects MH - Tumor Necrosis Factor-alpha/metabolism PMC - PMC5233570 OTO - NOTNLM OT - acute exacerbations of COPD (AECOPD) OT - chronic obstructive pulmonary disease (COPD) OT - influenza OT - respiratory virus OT - small airways OT - beta-adrenoceptor EDAT- 2016/04/30 06:00 MHDA- 2017/04/15 06:00 PMCR- 2016/04/10 CRDT- 2016/04/30 06:00 PHST- 2015/11/23 00:00 [received] PHST- 2016/02/23 00:00 [accepted] PHST- 2016/04/30 06:00 [entrez] PHST- 2016/04/30 06:00 [pubmed] PHST- 2017/04/15 06:00 [medline] PHST- 2016/04/10 00:00 [pmc-release] AID - CS20160093 [pii] AID - 10.1042/CS20160093 [doi] PST - ppublish SO - Clin Sci (Lond). 2016 May 1;130(10):829-37. doi: 10.1042/CS20160093. Epub 2016 Apr 10.