The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.
Proteases Induce Production of Thymic Stromal Lymphopoietin by Airway Epithelial Cells through Protease-Activated Receptor-2
Open accessAbstract
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-γ. 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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Thymic stromal lymphopoietin as a key initiator of allergic airway inflammation in mice
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How are TH2-type immune responses initiated and amplified?
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Metadata
- Authors
- Kouzaki, H., O'Grady, S. M., Lawrence, C. B., & Kita, H.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-07
- Volume
- 183
- Issue
- 2
- Pages
- 1427-1434
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1823764983
- Cited by
- 358
- References
- 57
- FWCI
- 17.12
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Kouzaki, H., O'Grady, S. M., Lawrence, C. B., & Kita, H. (2009). Proteases Induce Production of Thymic Stromal Lymphopoietin by Airway Epithelial Cells through Protease-Activated Receptor-2. The Journal of Immunology. https://doi.org/10.4049/jimmunol.0900904
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