Daidzein-Stimulated Increase in the Ciliary Beating Amplitude via an [Cl(−)](i) 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(−)](i) and enhanced CBD in cHNECs. The CBD increase that was stimulated by daidzein was mimicked by Cl(−)-free NO(3)(−) solution and bumetanide (an inhibitor of Na(+)/K(+)/2Cl(−) cotransport), both of which decreased [Cl(−)](i.) Moreover, the CBD increase was inhibited by 5-Nitro-2-(3-phenylpropylamino)benzoic acid (NPPB, a Cl(−) channel blocker), which increased [Cl(−)](i). CBF was also decreased by NPPB. The rate of [Cl(−)](i) decrease evoked by Cl(−)-free NO(3)(−) 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(−)](i) 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(−)](i), stimulated CBD increase in cHNECs at 37 °C. CBD is a crucial factor that can increase ciliary transport in the airways under physiological conditions.