Thiol-Mediated Regulation of ICAM-1 Expression in Endotoxin-Induced Acute Lung Injury

摘要: The intracellular redox state regulates several aspects of cell function, suggesting that strategies directed toward altering the cellular may modulate activation in inflammatory states. As most abundant thiol, glutathione plays a critical role as an buffer. Using diethylmaleate (DEM) glutathione-depleting agent, we evaluated effects GSH depletion rodent model polymorphonuclear neutrophil (PMN)-dependent acute lung injury. Rats received 500 μg LPS by intratracheal challenge, inducing 5.5-fold increase permeability and sixfold PMN content. Pretreatment with DEM prevented LPS-induced influx permeability. Northern analysis immunohistochemical studies suggest this effect be mediated preventing up-regulation ICAM-1 mRNA protein expression. This is specific to ICAM-1, because cytokine-induced chemoattractant TNF-α levels are unaffected. finding not unique lung, similar on was recapitulated chemical peritonitis. Further, vitro demonstrated pretreatment HUVEC monolayers both transendothelial migration. These data indicate presence thiol-sensitive mechanism for modulating gene expression potential novel therapeutic strategy diseases characterized PMN-mediated tissue