responsiveness of nasal ciliated cell for extra- or intracellular ionic environmental change

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09325
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Yasuda Makoto 京都府立医科大学, 医学(系)研究科(研究院), 講師 (60433273)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 線毛運動 / 鼻粘膜上皮細胞 / 細胞内イオン環境 / 細胞内クロライドイオン濃度 / CBF / CBA

Outline of Final Research Achievements

The functional activities of beating cilia are assessed by their frequency and the amplitude. Nasal ciliary beating is controlled by intracellular ions (Ca2+, H+ and Cl－), and is enhanced by a decreased concentration of intracellular Cl－ ([Cl－]i) in ciliated human nasal epithelial cells (cHNECs) in primary culture, which increases the ciliary beat amplitude. A novel method to measure both ciliary beat frequency (CBF) and ciliary beat distance (CBD)in cHNECs has been developed, which revealed that a decrease in [Cl－]i increased CBD, but not CBF, and an increase in [Cl－]i decreased both CBD and CBF. Thus, [Cl－]i inhibits ciliary beating in cHNECs, suggesting that axonemal structures controlling CBD and CBF may have Cl－ sensors and be regulated by [Cl－]i. These observations indicate that the activation of Cl－ secretion stimulates ciliary beating (increased CBD) mediated via a decrease in [Cl－]i in cHNECs. Thus, [Cl－]i is critical for controlling ciliary beating in cHNECs.

Free Research Field

耳鼻咽喉科

Academic Significance and Societal Importance of the Research Achievements

線毛運動は健全な鼻粘膜線毛輸送系を担う重要な細胞である。また線毛細胞を標的にした治療法はいまだにほとんど開発されておらず、未開拓の分野である。今回我々は細胞内クロライドイオン濃度の変化で線毛運動が変化することを示した。この制御機構をさらに詳細に研究することにより線毛運動の制御機構が明らかにできる。また細胞内クロライドイオンの低下を来たす薬剤を開発することにより線毛運動を活性化できる可能性が示唆された。慢性副鼻腔炎やアレルギー性鼻炎などの上気道炎症性疾患における今後の新たな薬剤開発のターゲットの一つになりうると考えられる。