The cholesterol-depleting agent MCD, known to disrupt the structure of caveolae/lipid rafts, was used to assess the role of caveolae/lipid rafts in cytokine-induced CAM expression in retinal endothelial cells. MCD pretreatment of hRVE cells downregulated TNF- –induced phosphorylation of inhibitor of NF-kappa B alpha (I B ) (Fig. 5A) and ICAM-1 expression (Fig.5B). In contrast, TNF- –triggered ERK phosphorylation was not affected. A similar effect was observed with IL-1 –medi-ated I B phosphorylation and ICAM-1 expression in response to MCD treatment (data not shown). These data suggest that the integrity of caveolae/lipid rafts is required for cytokine–