Toluene diisocyanate enhances human bronchial epithelial cells' permeability partly through the vascular endothelial growth factor pathway

Summary Background Toluene diisocyanate (TDI) is a recognized chemical asthmogen; yet, the mechanisms of its toxicity have not been elucidated. Objective To investigate the influence of TDI on the permeability of human bronchial epithelial cell (HBE; HBE135‐E6E7) monolayers in vitro, and the expression of vascular endothelial growth factor (VEGF) in these cells. Methods TDI–human serum albumin (HSA) conjugates were prepared by a modification of Son's method. Fluorescein isothiocyanate‐labelled dextran and transmission electron microscopy were used to evaluate the effects of TDI–HSA on HBE135‐E6E7 permeability. RT‐PCR and ELISA were used to evaluate VEGF gene expression and protein release from HBE135‐E6E7 cells stimulated by TDI–HSA. A VEGF‐neutralizing antibody was used in monolayer permeability experiments to determine the role of the VEGF pathway in this process. Results TDI–HSA significantly increased the permeability coefficients of HBE135‐E6E7 monolayers (P