Divergent Pathways of Gene Expression Are Activated by the RAGE Ligands S100b and AGE-BSA

Activation of the receptor for advanced glycation end products (RAGE) reportedly triggers a variety of proin-flammatory responses. However, our previous work re-vealed that RAGE-binding AGEs free of endotoxin were incapable of inducing vascular cell adhesion molecule-1 (VCAM-1) or tumor necrosis factor- (TNF-) expres-sion. Thus, the objective of this study was to clarify the role of AGEs in cell activation through gene expression profiling using both in vitro and in vivo model systems. Endothelial cells treated with AGE-BSA, previously shown to bind RAGE with high affinity, did not show gene expression changes indicative of an inflammatory response. In contrast, the alternate RAGE ligand, S100b, triggered an increase in endothelial mRNA ex-pression of a variety of immune-related genes. Th