Background
Chronic obstructive pulmonary disease (COPD) is characterized by a progressive airflow limitation in response to airway inflammation, causing bronchitis, small airway remodelling and emphysema. Currently, no curative therapies are available due to the largely unknown pathogenesis of COPD. Epithelial progenitor cells of the distal lung play a key role in specific regenerative functions, which are deregulated in COPD and contribute to remodelling and emphysema. Signals from the local microenvironment trigger these cells to become active and are largely derived from pulmonary fibroblasts, which are known to secrete cytokines, chemokines, growth factors and extra-cellular-matrix proteins. However, the relation between fibroblasts and epithelial progenitor cells in COPD is poorly understood. We aimed to investigate how pro-inflammatory environment affects the fibroblast/epithelial progenitor cells interplay and contributes to impaired lung repair.

Hypothesis
We hypothesized that IL-1β, as an inflammatory trigger, promotes a hostile microenvironment and impairs lung repair by disrupting the relation between fibroblast and epithelial progenitor cells.

Methods
MRC-5 fibroblasts or primary bronchial epithelial cells (PBECs) in air-liquid interface cultures alone, or their co-cultures were exposed to IL-1β. Gene expression of inflammatory cytokines (IL-6 and IL-8), pro-fibrotic fibroblast-phenotype markers (Vimentin, Collagen-1 and TGFβ), epithelial cell-type markers (FOXJ1, p63, CC10, IVL and E-Cadherin), anti-oxidant related genes (HO-1 and NRF1), and remodelling markers (CTGF and WNT5B) were measured via RT-qPCR. IL-8 secretion was measured using ELISA.

Results
IL-1β induced significant upregulation of remodelling and pro-inflammatory markers in PBECs, which was alleviated in the co-culture with fibroblasts. Downregulation of remodelling, anti-oxidative and pro-fibrotic genes occurred in MRC-5s treated with IL-1β.In co-cultured with PBECs this downregulation was not observed, but CTGF was upregulated.

Conclusion
Our results suggest fibroblasts exert a protective effect on epithelial cells during pro-inflammatory stimulation, but the role of epithelial cells on fibroblasts is more nuanced and possibly opposing.