ArticleJournal of immunology (Baltimore, Md. : 1950)2009
Proteases induce production of thymic stromal lymphopoietin by airway epithelial cells through protease-activated receptor-2.
Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 165 papers.
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Who cites it
165 citing papers in PubMed, 358 citations in OpenAlex.
- Solitary chemosensory cells amplify eosinophilic inflammation via PAR-2 activation in house dust mite-sensitized allergic rhinitis.The World Allergy Organization journal · 2026Article
- Genetic diversity of Collaborative Cross mice implicates FFAR3 as a target for ILC2 anti-inflammatory reprogramming.Nature communications · 2026Article
- Innate airway immune response to fungal allergens.Frontiers in immunology · 2026Review
- Alarmin Levels and Gastroesophageal Reflux Disease in Children: Significant Elevation of Thymic Stromal Lymphopoietin.Pediatric reports · 2025Article
- Article
- Is Nasal Dysbiosis a Required Component for Neuroinflammation in Major Depressive Disorder?Molecular neurobiology · 2025Review
- Epithelial-derived cytokines in the pathogenesis of severe asthma.Frontiers in allergy · 2025Review
- Thymic Stromal Lymphopoietin (TSLP): Evidence in Respiratory Epithelial-driven Diseases Including Chronic Rhinosinusitis with Nasal Polyps.Current allergy and asthma reports · 2024Review
- Epithelial sensing in allergic disease.Current opinion in immunology · 2024Review
- Review
- Review
- House dust mites stimulate thymic stromal lymphopoietin production in human bronchial epithelial cells and promote airway remodeling through activation of PAR2 and ERK signaling pathway.Scientific reports · 2024Article
- Regulation of Airway Epithelial-Derived Alarmins in Asthma: Perspectives for Therapeutic Targets.Biomedicines · 2024Review
- The New Paradigm: The Role of Proteins and Triggers in the Evolution of Allergic Asthma.International journal of molecular sciences · 2024Review
- 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
- Multifactorial Causes and Consequences of TLSP Production, Function, and Release in the Asthmatic Airway.Biomolecules · 2024Review
- Site-Specific Transient Receptor Potential Channel Mechanisms and Their Characteristics for Targeted Chronic Itch Treatment.Biomolecules · 2024Review
- ATP functions as a primary alarmin in allergen-induced type 2 immunity.American journal of physiology. Cell physiology · 2023Review
- Novel mechanistic insights underlying fungal allergic inflammation.PLoS pathogens · 2023Review
- Purification and characterization of a serine protease from organic dust and elucidation of its inductive effects on lung inflammatory mediators.American journal of physiology. Lung cellular and molecular physiology · 2023Article
105 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Thymic stromal lymphopoietin (TSLP) is produced by epithelial cells and triggers dendritic cell-mediated Th2-type inflammation. Although TSLP is up-regulated in epithelium of patients with asthma, the factors that control TSLP production have not been studied extensively. Because mouse models suggest roles for protease(s) in Th2-type immune responses, we hypothesized that proteases from airborne allergens may induce TSLP production in a human airway epithelial cell line, BEAS-2B. TSLP mRNA and protein were induced when BEAS-2B cells were exposed to prototypic proteases, namely, trypsin and papain. TSLP induction by trypsin required intact protease activity and also a protease-sensing G protein-coupled receptor, protease-activated receptor (PAR)-2; TSLP induction by papain was partially dependent on PAR-2. In humans, exposure to ubiquitous airborne fungi, such as Alternaria, is implicated in the development and exacerbation of asthma. When BEAS-2B cells or normal human bronchial epithelial cells were exposed to Alternaria extract, TSLP was potently induced. The TSLP-inducing activity of Alternaria was partially blocked by treating the extract with a cysteine protease inhibitor, E-64, or by infecting BEAS-2B cells with small interfering RNA for PAR-2. Protease-induced TSLP production by BEAS-2B cells was enhanced synergistically by IL-4 and abolished by IFN-gamma. These findings demonstrate that TSLP expression is induced in airway epithelial cells by exposure to allergen-derived proteases and that PAR-2 is involved in the process. By promoting TSLP production in the airways, proteases associated with airborne allergens may facilitate the development and/or exacerbation of Th2-type airway inflammation, particularly in allergic individuals.
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