ArticleRespiratory research2016
Extracellular ATP is involved in dsRNA-induced MUC5AC production via P2Y2R in human airway epithelium.
Article in Respiratory research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Transactivation of receptor tyrosine kinases by purinergic P2Y and adenosine receptors.Purinergic signalling · 2023Pooled it
- Live imaging of human airway epithelial repair in precision-cut lung slices after targeted cell damage.Biochemistry and biophysics reports · 2026Article
- Article
- Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia.Nature communications · 2025Article
- Mitochondrial damage-associated molecular patterns in chronic obstructive pulmonary disease: Pathogenetic mechanism and therapeutic target.Journal of translational internal medicine · 2023Article
- Intercellular Communication in Airway Epithelial Cell Regeneration: Potential Roles of Connexins and Pannexins.International journal of molecular sciences · 2023Review
- Anti-inflammatory effects of medications used for viral infection-induced respiratory diseases.Respiratory investigation · 2023Review
- Extracellular Nucleotides and Histamine Suppress TLR3- and RIG-I-Mediated Release of Antiviral IFNs from Human Airway Epithelial Cells.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Polyphosphate in Antiviral Protection: A Polyanionic Inorganic Polymer in the Fight Against Coronavirus SARS-CoV-2 Infection.Progress in molecular and subcellular biology · 2022Article
- Cytokine Storm and Mucus Hypersecretion in COVID-19: Review of Mechanisms.Journal of inflammation research · 2021Review
- Rhinovirus-16 increases ATP release in A549 cells without concomitant increase in production.ERJ open research · 2020Article
- Tiotropium and Fluticasone Inhibit Rhinovirus-Induced Mucin Production via Multiple Mechanisms in Differentiated Airway Epithelial Cells.Frontiers in cellular and infection microbiology · 2020Article
- Respiratory Cilia as a Therapeutic Target of Phosphodiesterase Inhibitors.Frontiers in pharmacology · 2020Review
- P2 Receptors as Therapeutic Targets in the Salivary Gland: From Physiology to Dysfunction.Frontiers in pharmacology · 2020Review
- Extracellular adenosine triphosphate is associated with airflow limitation severity and symptoms burden in patients with chronic obstructive pulmonary disease.Scientific reports · 2019Article
- Connexin Communication Compartments and Wound Repair in Epithelial Tissue.International journal of molecular sciences · 2018Review
- Oxidative stress enhances the expression of IL-33 in human airway epithelial cells.Respiratory research · 2018Article
- The Role of ErbB Receptors in Infection.Trends in microbiology · 2017Review
- High mucin 5AC expression predicts adverse postoperative recurrence and survival of patients with clear-cell renal cell carcinoma.Oncotarget · 2017Article
- Purinergic Signaling in Mast Cell Degranulation and Asthma.Frontiers in pharmacology · 2017Review
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn response to tissue damage or inflammation, adenosine-5'-triphosphate (ATP) is released into the extracellular compartment and has been demonstrated to augment inflammation via purinergic P2 receptors (P2Rs). Recently, ATP has been shown to be increased in the airways of COPD patients. In the present study, we examined the possible involvement of extracellular ATP in airway mucus hypersecretion during viral-induced COPD exacerbations.
methodsThe involvement of extracellular ATP in the release of a major airway mucin, MUC5AC, and its signal pathway was examined after stimulation with polyinosine-polycytidylic acid [poly(I:C)], a synthetic analog of dsRNA to mimic viral infection, and rhinovirus (RV) infection in NCI-H292 cells and differentiated airway epithelial cells from COPD patients.
resultsTreatment with poly(I:C) significantly increased the amount of extracellular ATP and induced MUC5AC release in NCI-H292 cells. Pre-treatment with a pannexin channel inhibitor, carbenoxolone (CBX), reduced the amount of extracellular ATP and suppressed MUC5AC release from poly(I:C)-treated cells. Pre-treatment with the P2R antagonist suramin significantly reduced the expression and release of MUC5AC. The inhibitory effects of CBX and suramin on the release of ATP and/or MUC5AC were replicated with RV infection. Pre-treatment with suramin also significantly reduced the expression and amount of extracellular EGFR ligands and the phosphorylation of EGFR and ERK in poly(I:C)-treated cells. In addition, pre-treatment with a P2Y2 receptor siRNA significantly suppressed the poly(I:C)-potentiated EGFR ligands and MUC5AC release. After poly(I:C) stimulation, the expression of MUC5AC in the differentiated cells from COPD patients was significantly higher than those from healthy subjects and the values of MUC5AC expression were inversely related with forced expiratory volume in 1 s (FEV1) % predicted. The inhibitory effects of CBX and suramin on poly(I:C)-potentiated MUC5AC expression were confirmed in differentiated airway epithelium from COPD patients.
conclusionsThese results demonstrate that dsRNA induces the release of ATP via pannexin channel and that the extracellular ATP is involved in the expression and release of MUC5AC, mainly via P2Y2R, in an autocrine manner. Modulation of this pathway could be a therapeutic target for viral-induced mucus hypersecretion in COPD exacerbations.
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