Document Detail

Proteases induce production of thymic stromal lymphopoietin by airway epithelial cells through protease-activated receptor-2.
MedLine Citation:
PMID:  19561109     Owner:  NLM     Status:  MEDLINE    
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.
Hideaki Kouzaki; Scott M O'Grady; Christopher B Lawrence; Hirohito Kita
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-06-26
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  183     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-07-07     Completed Date:  2009-09-15     Revised Date:  2014-09-11    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1427-34     Citation Subset:  AIM; IM    
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MeSH Terms
Allergens / pharmacology
Cell Line
Cytokines / biosynthesis*,  genetics
Epithelial Cells / metabolism*
Papain / pharmacology
Peptide Hydrolases / pharmacology*
RNA, Messenger / biosynthesis
Receptor, PAR-2 / physiology*
Respiratory System / cytology,  metabolism*
Transcriptional Activation*
Trypsin / pharmacology
Grant Support
Reg. No./Substance:
0/Allergens; 0/Cytokines; 0/RNA, Messenger; 0/Receptor, PAR-2; 0/thymic stromal lymphopoietin; EC 3.4.-/Peptide Hydrolases; EC; EC

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