Muscarinic receptor subtype-specific effects on cigarette smoke-induced inflammation in mice
| العنوان: | Muscarinic receptor subtype-specific effects on cigarette smoke-induced inflammation in mice |
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| المؤلفون: | Huib A. M. Kerstjens, Herman Meurs, Reinoud Gosens, J. Wess, Pieter S. Hiemstra, Martijn C. Nawijn, Loes E. M. Kistemaker, Machteld N. Hylkema, Isabella Bos |
| المساهمون: | Molecular Pharmacology, Faculteit Medische Wetenschappen/UMCG, Reproductive Origins of Adult Health and Disease (ROAHD), Groningen Research Institute for Asthma and COPD (GRIAC), Groningen Research Institute of Pharmacy |
| المصدر: | European Respiratory Journal, 42(6), 1677-1688. EUROPEAN RESPIRATORY SOC JOURNALS LTD European Respiratory Journal, 42(6), 1677-1688 |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, Chemokine, Genotype, medicine.medical_treatment, Inflammation, PHARMACOLOGICAL-PROPERTIES, OBSTRUCTIVE PULMONARY-DISEASE, TIOTROPIUM BROMIDE, Cholinergic Antagonists, ACETYLCHOLINE-RECEPTOR, Mice, AIRWAY SMOOTH-MUSCLE, Internal medicine, Muscarinic acetylcholine receptor, medicine, BRONCHIAL EPITHELIAL-CELLS, Animals, Receptor, MURINE AIRWAYS, Mice, Knockout, Receptor, Muscarinic M3, Receptor, Muscarinic M2, biology, business.industry, Gene Expression Profiling, Receptor, Muscarinic M1, Smoking, Muscarinic acetylcholine receptor M3, Muscarinic acetylcholine receptor M2, IN-VITRO, Acetylcholine, Mice, Inbred C57BL, Endocrinology, Cytokine, NONNEURONAL CHOLINERGIC SYSTEM, Gene Expression Regulation, biology.protein, medicine.symptom, business, CHEMOTACTIC ACTIVITY, Bronchoalveolar Lavage Fluid, medicine.drug |
| الوصف: | Cholinergic tone contributes to airflow obstruction in chronic obstructive pulmonary disease. Accordingly, anticholinergics are effective bronchodilators by blocking the muscarinic M-3 receptor on airway smooth muscle. Recent evidence indicates that acetylcholine also contributes to airway inflammation. However, which muscarinic receptor subtype(s) regulates this process is unknown.In this study, the contribution of the M-1, M-2 and M-3 receptor subtypes to cigarette smoke-induced airway inflammation was investigated by exposing muscarinic receptor subtype deficient mice to cigarette smoke for 4 days.In wild-type mice, cigarette smoke induced an increase in macrophages, neutrophils and lymphocytes in bronchoalveolar lavage fluid. Neutrophilic inflammation was higher in M-1(-/-) and M-2(-/-) mice compared to wild-type mice, but lower in M-3(-/-) mice. Accordingly, the release of keratinocyte-derived chemokine (KC), monocyte chemotactic protein-1 and interleukin-6 was higher in M-1(-/-) and M-2(-/-) mice, and reduced in M-3(-/-) mice. Markers of remodelling were not increased after cigarette smoke exposure. However, M-3(-/-) mice had reduced expression of transforming growth factor-beta 1 and matrix proteins. Cigarette smoke-induced inflammatory cell recruitment and KC release were also prevented by the M-3-receptor selective antagonist 1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP) in wild-type mice.Collectively, our data indicate a pro-inflammatory role for the M-3 receptor in cigarette smoke-induced neutrophilia and cytokine release, yet an anti-inflammatory role for M-1 and M-2 receptors. |
| تدمد: | 1399-3003 0903-1936 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3db6943f6a780b56704d6ea2b9d028a9 https://pubmed.ncbi.nlm.nih.gov/23397297 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3db6943f6a780b56704d6ea2b9d028a9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13993003 09031936 |
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