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Cited by 358

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 access
Kouzaki, Hideaki, O'Grady, Scott M, Lawrence, Christopher B, Kita, Hirohito·2009·The Journal of Immunology

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-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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Metadata

Authors
Kouzaki, H., O'Grady, S. M., Lawrence, C. B., & Kita, H.
Venue
The Journal of Immunology
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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CoChat. (2026). Citation check: Proteases Induce Production of Thymic Stromal Lymphopoietin by Airway Epithelial Cells through Protease-Activated Receptor-2. https://app.cochat.ai/papers/10.4049/jimmunol.0900904
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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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