ArticleRespiratory research2010
Pro-inflammatory mechanisms of muscarinic receptor stimulation in airway smooth muscle.
Article in Respiratory research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 75 citations in OpenAlex.
- Safety and Adverse Events after Targeted Lung Denervation for Symptomatic Moderate to Severe Chronic Obstructive Pulmonary Disease (AIRFLOW). A Multicenter Randomized Controlled Clinical Trial.American journal of respiratory and critical care medicine · 2019Trial
- Safety and Dose Study of Targeted Lung Denervation in Moderate/Severe COPD Patients.Respiration; international review of thoracic diseasesTrial
- Breaking the bottleneck of asthma treatment: the future of omni-targeted therapy.Journal of advanced research · 2026Review
- Secoisolariciresinol diglucoside ameliorates muscarinic acetylcholine receptor mediated activation of NLRP3 inflammasome in cardiomyocytes.Molecular biology reports · 2026Article
- Autonomic nervous system dysfunction in chronic obstructive pulmonary disease: mechanistic insights and therapeutic implications.Annals of medicine · 2025Review
- The Roles of Acetylcholine and Muscarinic Receptors in Allergic Rhinitis: Mechanisms, Clinical Insights and Future Directions.Current allergy and asthma reports · 2025Review
- L-Arginine and Intermittent Hypoxia Are Stress-Limiting Factors in Male Wistar Rat Models.International journal of molecular sciences · 2024Article
- Review
- cAMP-PDE signaling in COPD: Review of cellular, molecular and clinical features.Biochemistry and biophysics reports · 2023Review
- Potential antiproliferative and apoptotic effects of pilocarpine combined with TNF alpha in chronic myeloid leukemia cells.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- PD 102807 Induces M3 mAChR-Dependent GRK-/Arrestin-Biased Signaling in Airway Smooth Muscle Cells.American journal of respiratory cell and molecular biology · 2022Article
- Neuroimmune Pathophysiology in Asthma.Frontiers in cell and developmental biology · 2021Review
- The mode of action of anticholinergics in asthma.The European respiratory journal · 2018Review
- Novel water-soluble lignin derivative BP-Cx-1: identification of components and screening of potential targetsOncotarget · 2018Article
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- Article
- Acetylcholine Inhibits Monomeric C-Reactive Protein Induced Inflammation, Endothelial Cell Adhesion, and Platelet Aggregation; A Potential Therapeutic?Frontiers in immunology · 2018Article
- The novel compound Sul-121 inhibits airway inflammation and hyperresponsiveness in experimental models of chronic obstructive pulmonary disease.Scientific reports · 2016Article
- Crosstalk between beta-2-adrenoceptor and muscarinic acetylcholine receptors in the airway.Current opinion in pharmacology · 2014Review
- Genome-wide association mapping of acute lung injury in neonatal inbred mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAcetylcholine, the primary parasympathetic neurotransmitter in the airways, plays an important role in bronchoconstriction and mucus production. Recently, it has been shown that acetylcholine, by acting on muscarinic receptors, is also involved in airway inflammation and remodelling. The mechanism(s) by which muscarinic receptors regulate inflammatory responses are, however, still unknown.
methodsThe present study was aimed at characterizing the effect of muscarinic receptor stimulation on cytokine secretion by human airway smooth muscle cells (hASMc) and to dissect the intracellular signalling mechanisms involved. hASMc expressing functional muscarinic M2 and M3 receptors were stimulated with the muscarinic receptor agonist methacholine, alone, and in combination with cigarette smoke extract (CSE), TNF-α, PDGF-AB or IL-1β.
resultsMuscarinic receptor stimulation induced modest IL-8 secretion by itself, yet augmented IL-8 secretion in combination with CSE, TNF-α or PDGF-AB, but not with IL-1β. Pretreatment with GF109203X, a protein kinase C (PKC) inhibitor, completely normalized the effect of methacholine on CSE-induced IL-8 secretion, whereas PMA, a PKC activator, mimicked the effects of methacholine, inducing IL-8 secretion and augmenting the effects of CSE. Similar inhibition was observed using inhibitors of IκB-kinase-2 (SC514) and MEK1/2 (U0126), both downstream effectors of PKC. Accordingly, western blot analysis revealed that methacholine augmented the degradation of IκBα and the phosphorylation of ERK1/2 in combination with CSE, but not with IL-1β in hASMc.
conclusionsWe conclude that muscarinic receptors facilitate CSE-induced IL-8 secretion by hASMc via PKC dependent activation of IκBα and ERK1/2. This mechanism could be of importance for COPD patients using anticholinergics.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.