1,25-Dihydroxyvitamin D3 prevents toluene diisocyanate-induced airway epithelial barrier disruption
1,25-Dihydroxyvitamin D3 prevents toluene diisocyanate-induced airway epithelial barrier disruption
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1,25-二羟基维生素 D-3 可防止甲苯二异氰酸酯引起的气道上皮屏障破坏
DOI：
10.3892/ijmm.2015.2214
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发表时间：
2015-07-01
影响因子：
5.4
通讯作者：
Cai, Shaoxi
中科院分区：
文献类型：
--
作者：
Li, Wenjia;Dong, Hangming;Cai, Shaoxi
呼吸道上皮完整性的丧失在哮喘发病机制中起重要作用。有证据表明，维生素D在预防和治疗哮喘方面发挥着重要作用。然而，它在呼吸道上皮屏障功能中的作用仍不确定。我们之前已经在甲苯二异氰酸酯(TDI)诱导的哮喘模型中证明了上皮连接受损。在本研究中，我们假设1，25-二羟基维生素D-3[1，25(OH)(2)D-3]可能阻止TDI诱导的上皮屏障破坏。雄性BALB/c小鼠皮下致敏，然后用TDI攻击。然后，在TDI攻击之前，小鼠被给予1，25(OH)(2)D-3腹腔注射。体外培养16HBE支气管上皮细胞，用TDI-人血清白蛋白(HSA)刺激。结果显示，经1，25(OH)(2)D-3处理的小鼠的气道高反应性(AHR)降低，嗜中性粒细胞和嗜酸性粒细胞向呼吸道的浸润减少，细胞-细胞接触部位的E-钙粘附素和闭锁带1(ZO-1)表达增加。体外培养细胞暴露于TDI-HSA后，细胞跨上皮电阻(TER)迅速下降，细胞通透性增加，阻滞素表达减少，E-钙粘蛋白重新分布，同时细胞外信号调节蛋白(ERK)1/2水平显著上调。这些作用均可被1，25(OH)(2)D-3或ERK1/2抑制剂部分逆转。总之，我们的研究结果表明，1，25(OH)(2)D-3可以阻止TDI诱导的上皮屏障破坏，ERK1/2通路可能在这一过程中发挥作用。
The loss of airway epithelial integrity contributes significantly to asthma pathogenesis. Evidence suggests that vitamin D plays an important role in the prevention and treatment of asthma. However, its role in airway epithelial barrier function remains uncertain. We have previously demonstrated impaired epithelial junctions in a model of toluene diisocyanate (TDI)-induced asthma. In the present study, we hypothesized that 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] may prevent TDI-induced epithelial barrier disruption. Male BALB/c mice were dermally sensitized and then challenged with TDI. The mice were then administered 1,25(OH)(2)D-3 intraperitoneally prior to challenge with TDI. For in vitro experiments, 16HBE bronchial epithelial cells were cultured and stimulated with TDI-human serum albumin (HSA). The results revealed that the mice treated with 1,25(OH)(2)D-3 displayed decreased airway hyperresponsiveness (AHR), suppressed neutrophil and eosinophil infiltration into the airways, as well as an increased E-cadherin and zonula occludens-1 (ZO-1) expression at the cell-cell contact sites. In vitro, exposure of the cells to TDI-HSA induced a rapid decline in transepithelial electrical resistance (TER) and an increase in cell permeability, followed by a decrease in occludin expression and the redistribution of E-cadherin, accompanied by a significant upregulation in the levels of phosphorylated extracellular signal-regulated kinase (ERK)1/2. These effects were all partly reversed by treatment with either 1,25(OH)(2)D-3 or an ERK1/2 inhibitor. In conclusion, the findings of our study demonstrate that 1,25(OH)(2)D-3 prevents TDI-induced epithelial barrier disruption, and that the ERK1/2 pathway may play a role in this process.