Leukotriene B4 receptor 2 regulates the proliferation, migration, and barrier integrity of bronchial epithelial cells
Leukotriene B4 receptor 2 regulates the proliferation, migration, and barrier integrity of bronchial epithelial cells
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白三烯 B4 受体 2 调节支气管上皮细胞的增殖、迁移和屏障完整性
DOI：
10.1002/jcp.26455
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发表时间：
2018-08-01
影响因子：
5.6
通讯作者：
Yokomizo, Takehiko
中科院分区：
文献类型：
--
作者：
Liu, Min;Shen, Juan;Yokomizo, Takehiko
气道上皮细胞在哮喘的发病机制中起着至关重要的作用。白细胞三烯B4受体2（BLT 2）在气道上皮细胞上的功能尚不清楚。本研究通过转染BLT 2过表达质粒或BLT 2小干扰RNA（siRNA），对BLT 2在16 HBE支气管上皮细胞中的表达进行调控。然后将16 HBE细胞暴露于BLT 2拮抗剂（LY 255283）或BLT 2激动剂（12（S）-羟基十七碳-5Z，8 E，10 E-三烯酸[12-HHT]或CAY 10583）。结果显示，BLT 2过表达、12-HHT刺激或CAY 10583处理导致16 HBE细胞的增殖和迁移增强。此外，BLT 2表现出对上皮通透性的抑制作用，如通过测量跨上皮电阻（TER）和上皮通透性所示，以及对紧密连接蛋白（occludin和claudin-4）和磷酸化p38的水平的促进作用，如通过实时PCR和Western印迹分析所示。这些结果表明BLT 2是气道上皮屏障完整性的关键决定因素。相反，RNAi介导的敲除或LY 255283处理对增殖、迁移和上皮屏障完整性具有逆转作用。总之，我们的研究结果表明BLT 2对支气管上皮细胞功能的关键作用，BLT 2激动剂是治疗哮喘的潜在治疗药物。
The airway epithelium plays a crucial role in the pathogenesis of asthma. The functions of leukotriene B4 receptor 2 (BLT2) on the airway epithelial cells remains unknown. In our study, BLT2 expression in 16HBE bronchial epithelial cells were manipulated by transfection with BLT2 overexpression plasmid or BLT2 small interference RNA. 16HBE cells were then exposed to BLT2 antagonist (LY255283) or BLT2 agonist (12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid [12-HHT] or CAY10583). The results showed that BLT2 overexpression, 12-HHT stimulation, or CAY10583 treatment resulted in the enhanced proliferation and migration of 16HBE cells. In addition, BLT2 showed an inhibitory effect on epithelial permeability as illustrated by the measurement of transepithelial electrical resistance (TER) and epithelial permeability, and a promoting effect on the levels of tight junction proteins (occludin and claudin-4) and phosphorylated p38 as demonstrated by real-time PCR and Western blotting analyses. These results suggest BLT2 as a key determinant of airway epithelial barrier integrity. On the contrary, RNAi-mediated knockdown or LY255283 treatment had reversed effects on the proliferation, migration, and epithelial barrier integrity. Together, our findings suggest the critical roles of BLT2 on the functions of bronchial epithelial cells and that BLT2 agonists are potential therapeutic agents for asthma treatment.