IL-13 Augments Compressive Stress–Induced Tissue Factor Expression in Human Airway Epithelial Cells
Autor: | Jin-Ah Park, Stephanie A. Shore, Joo-Hyeon Lee, Jennifer A. Mitchel, Silvio Antoniak, David I. Kasahara, Elliot Israel, Maureen McGill, Sae Hoon Kim, Nigel Mackman, Scott H. Randell |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Ovalbumin medicine.medical_treatment Clinical Biochemistry Bronchi Thromboplastin 03 medical and health sciences Tissue factor 0302 clinical medicine Stress Physiological medicine Humans RNA Messenger Molecular Biology Cells Cultured Original Research Interleukin-13 biology medicine.diagnostic_test business.industry Epithelial Cells Cell Biology respiratory system respiratory tract diseases Cell biology 030104 developmental biology Cytokine Bronchoalveolar lavage 030228 respiratory system Interleukin 13 Immunology biology.protein Respiratory epithelium Bronchoconstriction medicine.symptom business Bronchoalveolar Lavage Fluid |
Zdroj: | American Journal of Respiratory Cell and Molecular Biology. 54:524-531 |
ISSN: | 1535-4989 1044-1549 |
Popis: | Tissue factor (TF) is best known as a cellular initiator of coagulation, but it is also a multifunctional protein that has been implicated in multiple pathophysiologic conditions, including asthma. In the lung, airway epithelial cells express TF, but it is unknown how TF expression is regulated by asthma-associated mediators. We investigated the role of IL-13, a type 2 cytokine, alone and in combination with compressive stress, which mimics asthmatic bronchoconstriction, on TF expression and release of TF-positive extracellular vesicles from primary normal human bronchial epithelial cells. Well-differentiated normal human bronchial epithelial cells were treated with IL-13 and compressive stress, alone and in combination. TF mRNA, protein and activity were measured in the cells and conditioned media. TF was also measured in the bronchoalveolar lavage (BAL) fluid of allergen-challenged mice and patients with asthma. IL-13 and compressive stress increased TF expression, but only compressive stress induced TF-positive extracellular vesicle release. Pretreatment with IL-13 augmented compressive stress–induced TF expression and release. TF protein and activity in BAL fluid were increased in allergen-sensitized and -challenged mice. TF was elevated in the BAL fluid of patients with mild asthma after an allergen challenge. Our in vitro and in vivo data indicate close cooperation between mechanical and inflammatory stimuli on TF expression and release of TF-positive extracellular vesicles in the lungs, which may contribute to pathophysiology of asthma. |
Databáze: | OpenAIRE |
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