ArticleImmunology2015
Proteinase activated receptor-2-mediated dual oxidase-2 up-regulation is involved in enhanced airway reactivity and inflammation in a mouse model of allergic asthma.
Article in Immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- A molecular systems architecture of asthma.Frontiers in immunology · 2026Pooled it
- Solitary chemosensory cells amplify eosinophilic inflammation via PAR-2 activation in house dust mite-sensitized allergic rhinitis.The World Allergy Organization journal · 2026Article
- Selective PAR2 Inhibition Attenuates HDM-Induced Th1/Th2 Responses in Human Epithelial and Murine Models of Allergic Rhinitis and Asthma.International forum of allergy & rhinology · 2025Article
- Nasal oxidative stress mediating the effects of colder temperature exposure on pediatric asthma symptoms.Pediatric research · 2024Article
- Airborne indoor allergen serine proteases and their contribution to sensitisation and activation of innate immunity in allergic airway disease.European respiratory review : an official journal of the European Respiratory Society · 2024Review
- Preparation and in vivo evaluation of nano sized cubosomal dispersion loaded with Ruta graveolens extracts as a novel approach to reduce asthma-mediated lung inflammation.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2024Article
- Association of single nucleotide polymorphisms in the F2RL1 gene with clinical and inflammatory characteristics of patients with asthma.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2024Article
- Diversification of PAR signaling through receptor crosstalk.Cellular & molecular biology letters · 2022Review
- Article
- Alternaria alternata-induced airway epithelial signaling and inflammatory responses via protease-activated receptor-2 expression.Biochemical and biophysical research communications · 2022Article
- TL1A/DR3 Axis, A Key Target of TNF-a, Augments the Epithelial-Mesenchymal Transformation of Epithelial Cells in OVA-Induced Asthma.Frontiers in immunology · 2022Article
- Targeting of protease activator receptor-2 (PAR-2) antagonist FSLLRY-NH2 as an asthma adjuvant therapy.Medicine · 2020Article
- Protease-Activated Receptors 2-Antagonist Suppresses Asthma by Inhibiting Reactive Oxygen Species-Thymic Stromal Lymphopoietin Inflammation and Epithelial Tight Junction Degradation.Allergy, asthma & immunology research · 2019Article
- Selective cleavage of fibrinogen by diverse proteinases initiates innate allergic and antifungal immunity through CD11b.The Journal of biological chemistry · 2019Article
- miR-155 Modulates Cockroach Allergen- and Oxidative Stress-Induced Cyclooxygenase-2 in Asthma.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Dual oxidase: a novel therapeutic target in allergic disease.British journal of pharmacology · 2018Review
- Glucose-6-phosphate dehydrogenase inhibition attenuates acute lung injury through reduction in NADPH oxidase-derived reactive oxygen species.Clinical and experimental immunology · 2018Article
- Oxidative Stress: Promoter of Allergic Sensitization to Protease Allergens?International journal of molecular sciences · 2017Review
- Oxidized CaMKII promotes asthma through the activation of mast cells.JCI insight · 2017Article
- Recent developments in the role of reactive oxygen species in allergic asthma.Journal of thoracic disease · 2017Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Airway epithelial cells (AECs) express a variety of receptors, which sense danger signals from various aeroallergens/pathogens being inhaled constantly. Proteinase-activated receptor 2 (PAR-2) is one such receptor and is activated by cockroach allergens, which have intrinsic serine proteinase activity. Recently, dual oxidases (DUOX), especially DUOX-2, have been shown to be involved in airway inflammation in response to Toll-like receptor activation. However, the association between PAR-2 and DUOX-2 has not been explored in airways of allergic mice. Therefore, this study investigated the contribution of DUOX-2/reactive oxygen species (ROS) signalling in airway reactivity and inflammation after PAR-2 activation. Mice were sensitized intraperitoneally with intact cockroach allergen extract (CE) in the presence of aluminium hydroxide followed by intranasal challenge with CE. Mice were then assessed for airway reactivity, inflammation, oxidative stress (DUOX-2, ROS, inducible nitric oxide synthase, nitrite, nitrotyrosine and protein carbonyls) and apoptosis (Bax, Bcl-2, caspase-3). Challenge with CE led to up-regulation of DUOX-2 and ROS in AECs with concomitant increases in airway reactivity/inflammation and parameters of oxidative stress, and apoptosis. All of these changes were significantly inhibited by intranasal administration of ENMD-1068, a small molecule antagonist of PAR-2 in allergic mice. Administration of diphenyliodonium to allergic mice also led to improvement of allergic airway responses via inhibition of the DUOX-2/ROS pathway; however, these effects were less pronounced than PAR-2 antagonism. The current study suggests that PAR-2 activation leads to up-regulation of the DUOX-2/ROS pathway in AECs, which is involved in regulation of airway reactivity and inflammation via oxidative stress and apoptosis.
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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.