ArticleMolecular and cellular biochemistry2013
Neutrophil elastase induces MUC5AC secretion via protease-activated receptor 2.
Article in Molecular and cellular biochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Synovial fluid biomarkers associated with osteoarthritis severity reflect macrophage and neutrophil related inflammation.Arthritis research & therapy · 2019Trial
- Higher levels of neutrophil extracellular traps in mucoid middle ear effusion obtained from otitis media with effusion in children.Annals of medicine · 2025Article
- Article
- Dipeptidyl peptidase-1 inhibitors in bronchiectasis.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Protease-activated receptor 1 in the pathogenesis of cystic fibrosis.BMJ open respiratory research · 2025Article
- Exacerbations of bronchiectasis.European respiratory review : an official journal of the European Respiratory Society · 2024Review
- Biomarkers in bronchiectasis.European respiratory review : an official journal of the European Respiratory Society · 2024Review
- Neutrophil-Derived Proteases in Lung Inflammation: Old Players and New Prospects.International journal of molecular sciences · 2024Review
- Inflammatory biomarkers and state of the tibiofemoral joint in the osteoarthritic knee: a narrative review.Annals of joint · 2024Review
- Flavonoids as inhibitors of human neutrophil elastase.Journal of enzyme inhibition and medicinal chemistry · 2021Review
- PAR-2-activated secretion by airway gland serous cells: role for CFTR and inhibition byAmerican journal of physiology. Lung cellular and molecular physiology · 2021Article
- Expression and Clinical Significance of Mucin Gene in Chronic Rhinosinusitis.Current allergy and asthma reports · 2020Review
- Polarization of protease-activated receptor 2 (PAR-2) signaling is altered during airway epithelial remodeling and deciliation.The Journal of biological chemistry · 2020Article
- Suhuang Antitussive Capsules-Ameliorative Effects on LPS-Induced Sputum Obstruction in Mice Through Promoting HGF Secretion.Frontiers in pharmacology · 2019Article
- Oxidative and endoplasmic reticulum stress in respiratory disease.Clinical & translational immunology · 2018Review
- Protease-activated receptor 2 activates airway apical membrane chloride permeability and increases ciliary beating.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Prophylactic inhibition of neutrophil elastase prevents the development of chronic neuropathic pain in osteoarthritic mice.Journal of neuroinflammation · 2017Article
- Association of Gel-Forming Mucins and Aquaporin Gene Expression With Hearing Loss, Effusion Viscosity, and Inflammation in Otitis Media With Effusion.JAMA otolaryngology-- head & neck surgery · 2017Article
- Neutrophil elastase stimulates MUC5AC expression in human biliary epithelial cells: a possible pathway of PKC/Nox/ROS.Archives of medical science : AMS · 2017Article
- Toxoplasma gondii serine-protease inhibitor-1: A new adjuvant candidate for asthma therapy.PloS one · 2017Article
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mucus hypersecretion is a major manifestation in patients with chronic inflammatory airway diseases, and mucin5AC (MUC5AC) protein is a major component of airway mucus. Previous studies have demonstrated that neutrophil elastase (NE) stimulates the secretion of MUC5AC from airway epithelial cells, however, the mechanism is poorly understood. NE is a known ligand for protein active receptors (PARs), which have been confirmed to participate in releasing MUC5AC in the airways. However, the role of PARs in NE-induced MUC5AC secretion remains unclear. We demonstrated that airway goblet-like Calu-3 cells express PAR1, PAR2, and PAR3 with a predominant level of PAR2. NE can increase PAR2 expression and MUC5AC release. In our study, we showed that NE binding to PAR2 can increase the cytosolic calcium concentration and subsequently activate PKC, leading to MUC5AC secretion. In order to investigate the mechanism of increased cytosolic calcium in Calu-3 cells, thapsigargin was used to exhaust the endoplasmic reticulum (ER) calcium pools, and 2-aminoethoxydiphenyl borate was used to inhibit the function of the store-operated calcium entry (SOCE) channels in the plasma membrane. We found that the NE-induced increase in intracellular calcium concentration is derived from release of the ER calcium pool and its subsequent calcium internal flux from the extracellular space via SOCE channels, which is dependent on sufficient levels of extracellular calcium.
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