The Secretome of Human Bronchial Epithelial Cells Exposed to Fine Atmospheric Particles Induces Fibroblast Proliferation

Abstract

Chronic exposure to particulate pollution is suspected to exacerbate inflammatory respiratory diseases such as asthma characterized by an airway remodelling involving fibrosis. Our study aims to investigate whether the secretome from human bronchial epithelial (HBE) cells exposed to fine particulate matter (PM) induces fibroblast proliferation. Primary HBE cells grown on air liquid interface were repeatedly exposed to fine PM at 5 and 10 µg/cm² (four treatments, 48 hours apart) and maintained in culture for five weeks. Collected basolateral culture medium was used as a conditioned medium for the subsequent treatment of fibroblasts. We observed that the conditioned medium collected from HBE cells treated with fine PM increased the growth rate of fibroblasts compared to the conditioned medium collected from control HBE cells. Fibroblast phenotype assessed by the observation of the vimentin network was well preserved. The mitogenic effect of conditioned medium was reduced in the presence of anti-epidermal growth factor receptor (EGFR), anti-amphiregulin or anti-TGFa, underlining the role of EGFR ligands in fibroblast proliferation. When fibroblasts were co-cultured with HBE cells treated once with fine PM, they exhibited a higher growth rate than fibroblasts co-cultured with non-treated HBE cells. Altogether these data show that the exposure of HBE cells to fine PM induced the production of EGFR ligands in sufficient amount to stimulate fibroblast proliferation providing insight into the role of PM in airway remodelling.