Muco-Obstructive Lung Disease Exhibits Distinct Hypoxic and Inflammatory Airway Epithelial Gene Pathways

We investigated how chronic airway epithelial hypoxia and inflammatory stimuli interact in human bronchial epithelial (HBE) cultures and resected human bronchiectatic lungs to produce the diseased epithelial environment characteristic of muco-obstructive diseases. HBE cultures were exposed to normoxia or hypoxia (1% O₂) for 4 days, and concurrently treated with supernatants from cystic fibrosis (CF) lung-derived mucopurulent material (SMM) or PBS for 5 days.

Bulk RNA-sequencing was perfomed. Results: Hypoxia and SMM regulated largely separate transcriptional programmes regardless of treatment order. PTGS2 (COX2) and CCL20 represented a small number of genes additively upregulated by both hypoxia and SMM.