Journal
EUROPEAN RESPIRATORY JOURNAL
Volume 34, Issue 6, Pages 1436-1443Publisher
EUROPEAN RESPIRATORY SOC JOURNALS LTD
DOI: 10.1183/09031936.00045209
Keywords
Airway smooth muscle cells; cigarette smoke; human; interleukin-8; muscarinic receptors
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Funding
- Boehringer Ingelheim Pharma GmbH, Biberach, Germany
- Dutch Organisation for Scientific Research (NWO) [916.86.036]
- Ministry of Science of the Islamic Republic of Iran, Tehran, Iran
- Canada Research Chairs Program
- Canadian Institutes of Health Research, Ontario, Canada
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Acetylcholine is the primary parasympathetic neurotransmitter in the airways and is known to cause bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine also regulates aspects of remodelling and inflammation through its action on muscarinic receptors. In the present study, we aimed to determine the effects of muscarinic receptor stimulation on cytokine production by human airway smooth muscle cells (primary and immortalised cell lines). The muscarinic receptor agonists carbachol and methacholine both induced modest effects on basal interleukin (IL)-8 and -6 secretion, whereas the secretion of RANTES, eotaxin, vascular endothelial growth factor-A and monocyte chemoattractant protein-1 was not affected. Secretion of IL-8 and -6 was only observed in immortalised airway smooth muscle cells that. express muscarinic M3 receptors,. In these cells, methacholine also significantly augmented IL-8 secretion in, combination with cigarette smoke extract in a synergistic, manner, whereas synergistic effects on IL-6 secretion were not significant. Muscarinic M3 receptors were the primary subtype, involved in augmenting cigarette smoke extract-induced IL-8 secretion, as only tiotropium bromide and muscarinic, M3 receptor subtype selective antagonists. abrogated the effects of methacholine. Collectively, these results indicate that muscarinic M3. receptor stimulation augments cigarette smoke extract-induced cytokine produc ion by airway smooth muscle. This interaction could be of importance in patients with chronic obstructive pulmonary, disease.
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