Cilia Stimulatory and Antibacterial Activities of T2R Bitter Taste Receptor Agonist Diphenhydramine: Insights into Repurposing Bitter Drugs for Nasal Infections.
Cilia Stimulatory and Antibacterial Activities of T2R Bitter Taste Receptor Agonist Diphenhydramine: Insights into Repurposing Bitter Drugs for Nasal Infections.
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DOI：
10.3390/ph15040452
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发表时间：
2022-04-06
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影响因子：
--
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气道运动纤毛中的T2R苦味受体增加纤毛搏动频率（CBF）和一氧化氮（NO）的产生。一些t2r的多态性与慢性鼻窦炎（CRS）和囊性纤维化（CF）的疾病结局有关。我们检测了在气液界面（ALI）培养的人鼻上皮细胞分化过程中纤毛T2Rs的表达。T2R表达随分化而增加，但在CF和非CF培养中无差异。铜绿假单胞菌鞭毛蛋白治疗降低了对苯海拉明应答的T2R14和40的表达。苯海拉明增加了NO的产生（通过荧光染料DAF-FM测量）和CBF（通过高速成像测量）。在鞭毛蛋白治疗后，CBF的增加被中断。苯海拉明抑制了实验室和临床菌株铜绿假单胞菌的生长，铜绿假单胞菌是CF和CF相关CRS的主要病原体。苯海拉明破坏铜绿假单胞菌的生物膜形成（通过结晶紫染色测量）以及铜绿假单胞菌与CF气道上皮细胞的表面附着（通过集落形成单位计数测量）。由于T2R激动剂苯海拉明增加NO生成和CBF，同时也减少细菌生长和生物膜生成，苯海拉明衍生化合物可能作为局部治疗在cf相关CRS中具有潜在的临床用途。然而，在铜绿假单胞菌感染的情况下，使用T2R激动剂作为治疗药物可能需要与抗炎药共同治疗以增强T2R表达。
T2R bitter taste receptors in airway motile cilia increase ciliary beat frequency (CBF) and nitric oxide (NO) production. Polymorphisms in some T2Rs are linked to disease outcomes in chronic rhinosinusitis (CRS) and cystic fibrosis (CF). We examined the expression of cilia T2Rs during the differentiation of human nasal epithelial cells grown at air–liquid interface (ALI). The T2R expression increased with differentiation but did not vary between CF and non-CF cultures. Treatment with Pseudomonas aeruginosa flagellin decreased the expression of diphenhydramine-responsive T2R14 and 40, among others. Diphenhydramine increased both NO production, measured by fluorescent dye DAF-FM, and CBF, measured via high-speed imaging. Increases in CBF were disrupted after flagellin treatment. Diphenhydramine impaired the growth of lab and clinical strains of P. aeruginosa, a major pathogen in CF and CF-related CRS. Diphenhydramine impaired biofilm formation of P. aeruginosa, measured via crystal violet staining, as well as the surface attachment of P. aeruginosa to CF airway epithelial cells, measured using colony-forming unit counting. Because the T2R agonist diphenhydramine increases NO production and CBF while also decreasing bacterial growth and biofilm production, diphenhydramine-derived compounds may have potential clinical usefulness in CF-related CRS as a topical therapy. However, utilizing T2R agonists as therapeutics within the context of P. aeruginosa infection may require co-treatment with anti-inflammatories to enhance T2R expression.
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影响因子：
3.1
作者：
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通讯作者：
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影响因子：
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