PM10 Exposure Impairs Differentiation and Induces Inflammation in Human Small Airway Epithelial Cells Cultured at the Air-Liquid Interface.

BACKGROUND

Particulate matter with an aerodynamic diameter ≤10 μm (PM10) is a major environmental pollutant implicated in chronic airway injury and remodeling. This study investigated the effects of chronic PM10 exposure on epithelial barrier integrity, cellular differentiation, surfactant expression, and inflammatory signaling in a human small airway epithelial air-liquid interface (ALI) model.

METHODS

Differentiated ALI cultures were exposed to PM10 for 7, 14, and 21 days. Transepithelial electrical resistance (TEER), epithelial lineage markers, surfactant proteins, inflammatory cytokines, and signaling pathways were analyzed using RT-PCR, ELISA, and western blotting.

RESULTS

PM10 exposure significantly reduced TEER over time indicating progressive epithelial barrier dysfunction. Club cell and ciliated cell markers decreased, whereas basal cell markers remained relatively preserved, suggesting impaired epithelial differentiation. Surfactant mRNA levels, particularly SP-A and SP-B, were reduced, while secreted SP-A paradoxically increased and SP-B secretion decreased. Pro-inflammatory cytokines, including IL-1β, IL-6, IL-8, and TNF-α, were significantly elevated. In addition, cleaved Notch1, Notch3, phosphorylated NF-κB and IκBα, and the downstream Notch targets HES1 and HEY1 were increased in PM10 -exposed cells.

CONCLUSION

Chronic PM10 exposure disrupts airway epithelial barrier integrity and impairs epithelial differentiation and function, accompanied by inflammatory activation through the Notch and NF-κB signaling pathways. These findings suggest a biologically plausible mechanistic link between environmental PM10 exposure and chronic airway epithelial dysfunction.