| DOI | Resolve DOI: https://doi.org/10.1165/rcmb.2013-0399OC |
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| Author | Search for: Cho, Seong H.; Search for: Lee, Sun H.; Search for: Kato, Atsushi; Search for: Takabayashi, Tetsuji; Search for: Kulka, Marianna1 ; Search for: Shin, Soon C.; Search for: Schleimer, Robert P. |
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| Name affiliation | - National Research Council Canada. Security and Disruptive Technologies
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| Format | Text |
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| Type | Article |
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| Journal title | American Journal of Respiratory Cell and Molecular Biology |
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| ISSN | 1044-1549
1535-4989 |
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| Volume | 52 |
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| Issue | 1 |
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| Pages | 88–95 |
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| Subject | plasminogen activator inhibitor-1; mast cells, epithelial cells; transforming growth factor-β1; chymase |
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| Abstract | Previous reports suggest that plasminogen activator inhibitor-1 (PAI-1) promotes airway remodeling and that human and mouse mast cells (MCs) are an important source of PAI-1. In the present study we investigated MC–epithelial cell (EC) interactions in the production of PAI-1. We stimulated the human MC line LAD2 with IgE-receptor cross-linking and collected the supernatants. We incubated the human bronchial EC line BEAS-2B with the LAD2 supernatants and measured the level of PAI-1. When the supernatants from IgE-stimulated LAD2 were added to BEAS-2B, there was a significant enhancement of PAI-1 production by BEAS-2B. When we treated the MC supernatants with a transforming growth factor (TGF)-β1 neutralizing antibody, the MC-derived induction of PAI-1 from BEAS-2B was completely abrogated. Although TGF-β1 mRNA was constitutively expressed in resting LAD2, it was not highly induced by IgE-mediated stimulation. Nonetheless, active TGF-β1 protein was significantly increased in LAD2 after IgE-mediated stimulation. Active TGF-β1 produced by primary cultured human MCs was significantly reduced in the presence of a chymase inhibitor, suggesting a role of MC chymase as an activator of latent TGF-β1. This study indicates that stimulation of human MCs by IgE receptor cross-linking triggers activation of TGF-β1, at least in part via chymase, which in turn induces the production of PAI-1 by bronchial ECs. Our data suggest that human MCs may play an important role in airway remodeling in asthma as a direct source of PAI-1 and by activating bronchial ECs to produce further PAI-1 via a TGF-β1–mediated activation pathway.l |
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| Publication date | 2015-01 |
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| Terms of use | |
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| Language | English |
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| Peer reviewed | Yes |
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| NPARC number | 23000820 |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction |
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Record identifier | 3ed19bf1-c6ad-4b53-b335-762e58d4c406 | | Record created | 2016-10-17 |
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| Record modified | 2016-10-17 |
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