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IL‐13 Augments Compression‐Induced Exosomal Tissue Factor Release from Bronchial Epithelial Cells
Author(s) -
Mitchel Jennifer,
Antoniak Silvio,
Kim SaeHoon,
McGill Maureen,
Randell Scott,
Shore Stephanie,
Mackman Nigel,
Park JinAh
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.863.21
Subject(s) - tissue factor , chemistry , exosome , bronchoconstriction , cytokine , microbiology and biotechnology , immunology , microvesicles , coagulation , asthma , biology , medicine , biochemistry , microrna , gene
Tissue factor (TF) is involved in multiple processes implicated in asthma, including coagulation, inflammation and angiogenesis. TF is released from well‐differentiated human bronchial epithelial (HBE) cells in response to mechanical compression mimicking asthmatic bronchospasm. Here we investigated the combined effect of mechanical compression and exposure to the Th2 cytokine, IL‐13, on the expression and release of TF from airway epithelial cells. Primary HBE cells were grown in air‐liquid interface (ALI) culture for 14‐17 days and were treated with IL‐13 or vehicle and exposed to a trans‐cellular pressure of 30 cmH 2 0 for 3 hours. The pro‐coagulant activity of basolateral media from HBE cells was significantly greater in compressed versus non‐compressed cells, and was TF‐dependent. Pretreatment of cells with IL‐13 augmented compression‐induced TF mRNA expression. Exposure to IL‐13 alone did not affect the release of TF, but pretreatment with IL‐13 augmented the compression‐induced release of TF. Released TF was exclusively contained in the exosome fraction isolated by ultracentrifugation. Lastly, the TF level and pro‐coagulant activity were significantly greater in BAL from mice challenged with ovalbumin versus PBS. Our data are consistent with the hypothesis that bronchoconstriction contributes to the generation of a lung microenvironment favoring asthma development. Compressive stress‐mediated production and release of active TF from airway epithelial cells was augmented in the presence of the Th2 cytokine, IL‐13.