Daidzein-Stimulated Increase in the Ciliary Beating Amplitude via an [Cl] Decrease in Ciliated Human Nasal Epithelial Cells.

The effects of the isoflavone daidzein on the ciliary beat distance (CBD, which is a parameter assessing the amplitude of ciliary beating) and the ciliary beat frequency (CBF) were examined in ciliated human nasal epithelial cells (cHNECs) in primary culture. Daidzein decreased [Cl] and enhanced CBD in cHNECs. The CBD increase that was stimulated by daidzein was mimicked by Cl-free NO₃ solution and bumetanide (an inhibitor of Na⁺/K⁺/2Cl cotransport), both of which decreased [Cl] Moreover, the CBD increase was inhibited by 5-Nitro-2-(3-phenylpropylamino)benzoic acid (NPPB, a Cl channel blocker), which increased [Cl]. CBF was also decreased by NPPB. The rate of [Cl] decrease evoked by Cl-free NO₃ solution was enhanced by daidzein. These results suggest that daidzein activates Cl channels in cHNECs. Moreover, daidzein enhanced the microbead transport driven by beating cilia in the cell sheet of cHNECs, suggesting that an increase in CBD enhances ciliary transport. An [Cl] decrease enhanced CBD, but not CBF, in cHNECs at 37 °C, although it enhanced both at 25 °C. Intracellular Cl affects both CBD and CBF in a temperature-dependent manner. In conclusion, daidzein, which activates Cl channels to decrease [Cl], stimulated CBD increase in cHNECs at 37 °C. CBD is a crucial factor that can increase ciliary transport in the airways under physiological conditions.