Background: Acute respiratory distress syndrome (ARDS) is characterized by overwhelming inflammatory responses\nand lung remodeling. We hypothesized that leukocyte infiltration during the inflammatory response modulates\nepithelial remodeling through a mechanism of epithelial-mesenchymal transition (EMT).\nMethods: Human lung epithelial cells were treated for 30 min with hydrochloric acid (HCl). Human monocytes\nwere then cocultured with the epithelial cells for up to 48 h, in the presence or absence of blocking peptides\nagainst lymphocyte function-associated antigen-1 (LFA-1), or tyrphostin A9, a specific inhibitor for platelet-derived\ngrowth factor (PDGF) receptor tyrosine kinase.\nResults: Exposure of lung epithelial cells to HCl resulted in increased expression of intercellular adhesion\nmolecule-1 (ICAM-1) and production of interleukin (IL)-8 at 24 h. The expression of the epithelial markers E-cadherin\ndecreased while the mesenchymal markers vimentin and ?-smooth muscle actin (?-SMA) increased at 24 h and\nremained high at 48 h. The addition of monocytes augmented the profiles of lower expression of epithelial markers\nand higher mesenchymal markers accompanied by increased collagen deposition. This EMT profile was associated\nwith an enhanced production of IL-8 and PDGF. Treatment of the lung epithelial cells with the LAF-1 blocking\npeptides CD11a237ââ?¬â??246 or/and CD18112ââ?¬â??122 suppressed monocyte adhesion, production of IL-8, PDGF and\nhydroxyproline as well as EMT markers. Treatment with tyrphostin A9 prevented the EMT profile shift induced\nby HCl stimulation.\nConclusions: The interaction between epithelial cells and monocytes enhanced epithelial remodelling after initial\ninjury through EMT signalling that is associated with the release of soluble mediators, including IL-8 and PDGF
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