Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
Int J Mol Sci. 2018 Nov 26;19(12):3754. doi: 10.3390/ijms19123754.
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.
大豆黄酮对人鼻纤毛上皮细胞（ciliated human nasal epithelial cells，cHNECs）纤毛摆动距离（ciliary beat distance，CBD，评估纤毛摆动幅度的参数）和纤毛摆动频率（cilary beat frequency，CBF）的影响在原代培养的 cHNECs 中进行了研究。大豆黄酮降低了 cHNECs 中的 [Cl]并增强了 CBD。大豆黄酮刺激的 CBD 增加可被无 Cl 的 NO₃溶液和布美他尼（Na⁺/K⁺/2Cl 共转运体抑制剂）模拟，两者均降低了 [Cl]。此外，CBD 增加被 5-硝基-2-(3-苯丙基氨基)苯甲酸（NPPB，Cl 通道阻滞剂）抑制，其增加了 [Cl]。CBF 也被 NPPB 降低。无 Cl 的 NO₃溶液引起的 [Cl]下降率被大豆黄酮增强。这些结果表明，大豆黄酮激活了 cHNECs 中的 Cl 通道。此外，大豆黄酮增强了 cHNECs 细胞层中纤毛摆动驱动的微球转运，表明 CBD 增加增强了纤毛转运。在 37°C 时，[Cl]的降低增强了 CBD，但不增强 CBF，而在 25°C 时则增强了两者。细胞内 Cl 以温度依赖的方式影响 CBD 和 CBF。总之，大豆黄酮通过激活 Cl 通道降低 [Cl]，刺激 37°C 时 cHNECs 的 CBD 增加。CBD 是在生理条件下增加气道纤毛运输的关键因素。
