Acrolein Induces Epithelial Injury and Remodeling Through Direct Activation of Src

Abstract

Cigarette smoke (CS)-derived reactive electrophiles such as acrolein affect biological systems largely by targeting redox-sensitive cysteine residues. In the present studies we examined the effects of acrolein exposure on the airway epithelium and importance of the redox-sensitive tyrosine kinase Src in these responses. Exposure of mouse tracheal epithelial (MTE) cells in Transwell® inserts to acrolein resulted in loss of trans-epithelial resistance (TER) and increased permeability to FITC-dextran, accompanied with a loss of epithelial junction proteins E-cadherin and zonal occludin-1 (ZO-1). These responses were prevented by pretreatment with the Src inhibitor PP2. Similar studies with human epithelial H292 cells indicated that inhibition of Src using PP2 or siRNA targeting prevented acrolein-induced phosphorylation of p120 and loss of E-cadherin. Acute exposure of C57BL/6 mice to acrolein (5 ppm for 4 hrs) increased epithelial permeability, measured by enhanced leakage of i.v. injected FITC-dextran into...