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

Lung implantable devices, such as stents and valves, are used as treatment for lung cancer and chronic obstructive pulmonary disease (COPD). They apply continuous compressive stress to airway tissue, potentially triggering adverse effects such as chronic inflammation, granulation tissue hyperplasia, and fibrosis at the implant site. 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. Confluent layers of bronchial epithelial cells (16HBE) were subjected to compressive stress using agarose-embedded weights (3, 6, 9, and 15 g). After 24 h, cell viability, inflammation, fibrosis, and mechano-transduction were assessed using cell viability assays, quantitative real-time PCR, ELISA, and immunofluorescent staining. Maximum compressive stress (15 g) led to reduced cell viability. Compression increased the expression of inflammation, CXCL8, TNF, IL1α, GM-CSF, and remodeling-related genes, EGR1, TNC, COL1A1, and CTGF, whereas no changes in TGFB1, TNC, and FN1 expression were observed. These changes were reflected in protein levels with increased CXCL8, IL-1α, and connective tissue growth factor (CTGF) in supernatant upon compression. Compressed cells showed increased actin polymerization, mechanoreceptor relocalization, and Yes-associated protein (YAP) nuclear translocation, reflecting a mechanotransducive response. 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.NEW & NOTEWORTHY Our research introduces a novel in vitro model to study how contact-compressive stress drives pathological wound-healing responses in bronchial epithelial cells. By linking mechanical loading to mechanosensory-redistribution, cytoskeletal remodeling, and both pro-inflammatory (CXCL8, IL6, IL1A, and GM-CSF) and profibrotic gene expression (CTGF, COL1A1, and EGR1), this work provides critical insights into the cellular mechanisms underlying lung implant-associated complications and offers a platform for future biomaterial and device testing.