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Leukotriene B4 receptor 2 regulates the proliferation, migration, and barrier integrity of bronchial epithelial cells
Author(s) -
Liu Min,
Shen Juan,
Yuan Huimin,
Chen Fengling,
Song Huaidong,
Qin Hui,
Li Yanqin,
Xu Jiabo,
Ye Qing,
Li Shenxian,
Saeki Kazuko,
Yokomizo Takehiko
Publication year - 2018
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.26455
Subject(s) - epithelium , transfection , tight junction , microbiology and biotechnology , leukotriene d4 , chemistry , occludin , gene knockdown , small interfering rna , respiratory epithelium , receptor , immunology , cell culture , biology , antagonist , biochemistry , genetics
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.