Contact-compression induces inflammatory and remodeling responses in bronchial epithelial cells

Aims and objectives: Lung implantable devices such as stents and valves are used for treatment of lung cancer and COPD. They apply continuous supraphysiological compressive stress to airway tissue, potentially triggering adverse effects such as chronic inflammation, granulation tissue hyperplasia and fibrosis at the implant site. In order to identify the biological responses underlying this process we developed an in vitro contact-compression model that applies variable compressive stress to bronchial epithelial cells. Methods: Confluent layers of bronchial epithelial cells (16HBE) were subjected to compressive stress using agarose-embedded weights (3g, 6g, 9g and 15g). After 24hrs, cell viability, inflammation, fibrosis and mechano-transduction were assessed using cell viability assays, qRT-PCR, ELISA and immunofluorescent staining. Results: Maximum compressive stress (15g) led to reduced cell viability. Compression increased the expression of inflammation, CXCL8, TNF, IL1α, GM-CSF, and remodeling-related genes, EGR1, TNC, COL1A1, CTGF, while no changes in TGFB1, TNC and FN1 expression were observed. These changes were reflected in protein levels with increased CXCL8, IL-1α and CTGF in supernatant upon compression. Compressed cells showed increased actin polymerization, mechanoreceptor re-localization, and YAP nuclear translocation, reflecting a mechanotransducive response. Conclusion: We developed a viable in vitro model to study contact-compression, showing biomechanical inflammatory and remodeling responses. With adjustable components, this model can be applied to further study tissue responses to lung implants.