These findings concerning ET-1-induced COX-2 expression and PGE2 generation imply that ET-1 might play a critical role in brain injury, vascular inflammation, and CNS disorders, mediated by c-Src-dependent transactivation of EGFR linking to MAPKs/AP-1 pathways in brain microvascular endothelial cells. Here, JUN is linked to central nervous system disorder.