Ginsenoside Rd promotes the expression of acetylated α-tubulin and FOXJ1 in human bronchial epithelial cells

Mucociliary clearance is an airway defense mechanism driven by the coordinated function of mucus and motile cilia. Although ciliary beat frequency (CBF) reflects the motile function of ciliated cells, the generation and maintenance of ciliated cells are also essential for sustained airway epithelial defense. Although short-term treatment with ginsenoside Rd (Rd) increases CBF, its long-term effects on the differentiation of human airway epithelial cells remain unclear. We investigated the effects of Rd on primary normal human bronchial epithelial cells cultured under air-liquid interface conditions. On day 10, Rd increased the percentage of acetylated α-tubulin (Ac-α-tubulin)-positive cells, whereas the percentage of MUC5AC-positive cells remained unchanged. Rd promoted the time-dependent increase in Ac-α-tubulin-positive cells, while LDH release or total cell number were not significantly altered. Long-term Rd treatment did not affect baseline CBF. Furthermore, perfusion with Rd increased CBF independent of differentiation conditions. These observations suggest that the increase in Ac-α-tubulin-positive cells by long-term Rd treatment and the increase in CBF by short-term Rd treatment may be functionally separable. The increase in the percentage of Ac-α-tubulin-positive cells was suppressed by ERβ inhibitors and CREB-dependent transcription inhibitors. Rd also increased the expression of FOXJ1 mRNA transcripts. These findings suggest that Rd may modulate the expression of ciliated cell markers, such as acetylated α-tubulin and FOXJ1, and ciliary motility in human airway epithelial cells.