The Role of Reactive Oxygen Intermediates in the Regulation of Cytokine-Induced ICAM-1 Surface Expression on Endothelial Cells

摘要

ICAM-1 upregulation by endothelial cells plays a pivotal role in many disease processes,but signalling mechanisms leading to increased expression are poorly understood.In the current study we investigated the regulatory capacity of reactive oxygen intermediates (ROIs) in ICAM-1 activation by stimulating endothilial cells with the pro-inflammatory cytokines IL-1#beta#,TNF#alpha#,IFN#gamma#,IL-2,and IL-4 prior to antioxidant treatment.ICAM-1 was expressed constitutively and upregulated on ECV304 by IL1-#beta#,IL2,and IFN#gamma#,and on SKHEP-1,by IFN#gamma#,IL1-#beta#,and TNF#alpha#. Phenanthroline (PHE) and disulfiram (DIS) showed the greatest ability to inhibit cytokine-stimulated ICAM-1 expression and in a dose-dependent manner.The #alpha#,#alpha#-diphenyl-#beta#-picrylhydrazyl (DPPH) conversion assay showed that PHE and DIS had zero ability to scavenge free radicals and thus no known antioxidant activity. However,both are knoen metal chelators and our findings therefore suggest a unique role for metal ions in the control of cytokine-induced ICAM-1 expression on endothelial cells.