Background: Chronic lung disorders involve pathological alterations with hypoxic milieus. Hypoxia may influence the release of inflammatory mediators and growth factors involved in disease pathology. The aim of this work was to investigate how hypoxia affects human lung epithelial cells in combination with profibrotic stimuli and its correlation to pathogenesis.

Methods: Human bronchial (BEAS-2B) and alveolar (hAELVi) epithelial cells were exposed to either hypoxia (1% O2) or normoxia (21% O2) for 24 h, with or without transforming growth factor (TGF)-b1. Gene and protein expressions related to disease pathology were analyzed with qPCR, multiplex and immunohistochemistry. Changes in cell viability were investigated.

Results: Hypoxia significantly downregulated genes related to mitochondrial stress, oxidative stress, apoptosis and inflammation, whereas VEGFR2 expression increased in both cell types. In BEAS-2B, hypoxia increased Tenascin-C, whereas both hypoxia and TGF-b1 increased the release of VEGF, IL-6, IL-8 and MCP-1. In hAELVi, hypoxia reduced the release of FGF, EGF, PGE2, IL-6 and IL-8, whereas TGF-b1 significantly increased the release of PGE2 and IL-6. TGF-b1 treated hAELVi showed a decreased release of PGE2 and IL-8 in hypoxia compared to normoxia. Metabolic activity was significantly increased in hypoxia exposed cells.

Conclusions: Bronchial and alveolar epithelial cells respond differently to hypoxia and profibrotic stimuli. The bronchial epithelium appears more responsive to changes in oxygen levels and remodeling processes compared to the alveoli, indicating that hypoxia is a potential driver of pathogenesis in chronic lung disorders.