Mechanism of E-cadherin redistribution in bronchial airway epithelial cells in a TDI-induced asthma model.

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.