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

ABSTRACT: 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?^- 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?^- 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.

SUBMITTER: Inui TA

PROVIDER: S-EPMC6321431 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Project description:BackgroundPrimary ciliary dyskinesia (PCD) is a rare congenital respiratory disorder characterized by abnormal ciliary motility leading to chronic airway infections. Qualitative evaluation of ciliary beat pattern based on digital high-speed videomicroscopy analysis has been proposed in the diagnosis process of PCD. Although this evaluation is easy in typical cases, it becomes difficult when ciliary beating is partially maintained. We postulated that a quantitative analysis of beat pattern would improve PCD diagnosis. We compared quantitative parameters with the qualitative evaluation of ciliary beat pattern in patients in whom the diagnosis of PCD was confirmed or excluded.MethodsNasal nitric oxide measurement, nasal brushings and biopsies were performed prospectively in 34 patients with suspected PCD. In combination with qualitative analysis, 12 quantitative parameters of ciliary beat pattern were determined on high-speed videomicroscopy recordings of beating ciliated edges. The combination of ciliary ultrastructural abnormalities on transmission electron microscopy analysis with low nasal nitric oxide levels was the "gold standard" used to establish the diagnosis of PCD.ResultsThis "gold standard" excluded PCD in 15 patients (non-PCD patients), confirmed PCD in 10 patients (PCD patients) and was inconclusive in 9 patients. Among the 12 parameters, the distance traveled by the cilium tip weighted by the percentage of beating ciliated edges presented 96% sensitivity and 95% specificity. Qualitative evaluation and quantitative analysis were concordant in non-PCD patients. In 9/10 PCD patients, quantitative analysis was concordant with the "gold standard", while the qualitative evaluation was discordant with the "gold standard" in 3/10 cases. Among the patients with an inconclusive "gold standard", the use of quantitative parameters supported PCD diagnosis in 4/9 patients (confirmed by the identification of disease-causing mutations in one patient) and PCD exclusion in 2/9 patients.ConclusionsWhen the beat pattern is normal or virtually immotile, the qualitative evaluation is adequate to study ciliary beating in patients suspected for PCD. However, when cilia are still beating but with moderate alterations (more than 40% of patients suspected for PCD), quantitative analysis is required to precise the diagnosis and can be proposed to select patients eligible for TEM.

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

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Dataset Information

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

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OmicsDI is part of the ELIXIR infrastructure

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