Mechanism of E-cadherin redistribution in bronchial airway epithelial cells in a TDI-induced asthma model
Mechanism of E-cadherin redistribution in bronchial airway epithelial cells in a TDI-induced asthma model
复制标题
TDI诱导哮喘模型支气管气道上皮细胞E-钙粘蛋白再分布机制
DOI：
10.1016/j.toxlet.2013.03.033
复制
发表时间：
2013-06-20
影响因子：
3.5
通讯作者：
Cai, Shaoxi
中科院分区：
文献类型：
--
作者：
Song, Jiafu;Zhao, Haijin;Cai, Shaoxi
上皮钙粘蛋白（epithelial cadherin，E-cadherin）是一种跨膜蛋白，为气道上皮提供了必要的结构和免疫功能，气道上皮是一种屏障结构，在哮喘发病机制中起着重要作用。甲苯二异氰酸酯（TDI）是目前职业性哮喘的主要原因之一。然而，相对较少的研究已经进行，以确定TDI对气道上皮屏障特性的生物学效应，但它是已知的，TDI可以在体外损伤气道上皮紧密连接。在这里，我们假设TDI可以损伤正常和过敏诱导的气道上皮细胞中的E-钙粘蛋白。为了验证这一点，我们开发了TDI诱导的哮喘小鼠模型，其特征在于嗜中性粒细胞为主的气道炎症，上皮脱落，和明显的异常分布的E-钙粘蛋白。地塞米松（DEX）预处理显着拯救E-钙粘蛋白的免疫反应性，伴随着增加中性粒细胞在支气管肺泡灌洗液（BALF）。在体外，TDI-人血清白蛋白（HSA）诱导的E-cadherin的再分布与细胞外信号调节激酶（ERK）1/2激活有关。DEX对磷酸化ERK（p-ERK）1/2的抑制可部分逆转该反应。这些结果表明，E-钙粘蛋白再分布可能是TDI诱导的哮喘的产生的重要贡献者。(c)2013爱思唯尔爱尔兰有限公司版权所有。
E-cadherin (epithelial cadherin), a transmembrane protein, provides essential architecture and immunological function to the airway epithelium, a barrier structure that plays an essential role in asthma pathogenesis. Toluene diisocyanate (TDI) is currently one of the leading causes of occupational asthma. However, relatively few studies have been undertaken to determine the biological effects of TDI on the barrier properties of airway epithelium, but it is known that TDI can damage airway epithelial tight junctions in vitro. Here, we hypothesize that TDI can injure E-cadherin both in normal and allergic-induced airway epithelium. To test this, we developed a murine model of TDI-induced asthma characterized by neutrophil-dominated airway inflammation, epithelial shedding, and obvious aberrant distribution of E-cadherin. Pretreatment with dexamethasone (DEX) significantly rescued the immunoreactivity of E-cadherin, accompanied by increased neutrophils in bronchoalveolar lavage fluid (BALF). In vitro, TDI-human serum albumin (HSA)-induced redistribution of E-cadherin was associated with extracellular signal-regulated kinase (ERK)1/2 activation. The inhibition of phospho-ERK (p-ERK)1/2 by DEX can partly reverse this reaction. These results indicate that E-cadherin redistribution may be an important contributor in the generation of TDI-induced asthma. (c) 2013 Elsevier Ireland Ltd. All rights reserved.