A Muscarinic Antagonist Reduces Airway Inflammation and Bronchoconstriction Induced by Ambient Particulate Matter in a Mouse Model of Asthma.

Autor:	Kurai J; Department of Respiratory Medicine and Rheumatology, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, Tottori 683-8504, Japan. kurajun@med.tottori-u.ac.jp., Watanabe M; Department of Respiratory Medicine and Rheumatology, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, Tottori 683-8504, Japan. watanabm@grape.med.tottori-u.ac.jp., Sano H; Department of Respiratory Medicine and Allergology, Kinki University, 377-2 Ohnohigashi, Osakasayama, Osaka 589-0014, Japan. hsano@med.kindai.ac.jp., Iwata K; Department of Respiratory Medicine and Rheumatology, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, Tottori 683-8504, Japan. iwatak@mfc.or.jp.; Mio Fertility Clinic, Reproductive Centre, 2-2-1 Kuzumo-Minami, Yonago, Tottori 683-0008, Japan. iwatak@mfc.or.jp., Hantan D; Department of Respiratory Medicine and Rheumatology, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, Tottori 683-8504, Japan. degu.jirefu@technopro.com., Shimizu E; Department of Respiratory Medicine and Rheumatology, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, Tottori 683-8504, Japan. shimizu.eiji@hmw.gr.jp.
Jazyk:	angličtina
Zdroj:	International journal of environmental research and public health [Int J Environ Res Public Health] 2018 Jun 06; Vol. 15 (6). Date of Electronic Publication: 2018 Jun 06.
DOI:	10.3390/ijerph15061189
Abstrakt:	Ambient particulate matter (PM) can increase airway inflammation and induce bronchoconstriction in asthma. This study aimed to investigate the effect of tiotropium bromide, a long-acting muscarinic antagonist, on airway inflammation and bronchoconstriction induced by ambient PM in a mouse model of asthma. We compared the effect of tiotropium bromide to that of fluticasone propionate and formoterol fumarate. BALB/c mice were sensitized to ovalbumin (OVA) via the airways and then administered tiotropium bromide, fluticasone propionate, or formoterol fumarate. Mice were also sensitized to ambient PM via intranasal instillation. Differential leukocyte counts and the concentrations of interferon (IFN)-γ, interleukin (IL)-5, IL-6, IL-13, and keratinocyte-derived chemokine (KC/CXCL1) were measured in bronchoalveolar lavage fluid (BALF). Diacron-reactive oxygen metabolites (dROMs) were measured in the serum. Airway resistance and airway inflammation were evaluated in lung tissue 24 h after the OVA challenge. Ambient PM markedly increased neutrophilic airway inflammation in mice with OVA-induced asthma. Tiotropium bromide improved bronchoconstriction, and reduced neutrophil numbers, decreased the concentrations of IL-5, IL-6, IL-13, and KC/CXCL1 in BALF. However, tiotropium bromide did not decrease the levels of dROMs increased by ambient PM. Though eosinophilic airway inflammation was reduced with fluticasone propionate, neutrophilic airway inflammation was unaffected. Bronchoconstriction was improved with formoterol fumarate, but not with fluticasone propionate. In conclusion, tiotropium bromide reduced bronchoconstriction, subsequently leading to reduced neutrophilic airway inflammation induced by ambient PM. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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