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Endothelial cells coordinate the recruitment of inflammatory cells to sites of vascular injury. Endothelial cells produce and release cytokines and growth factors serving as communication signals to leukocytes as well as with organs and tissues. In addition, endothelial cells respond to inflammatory stimuli such as lipopolysaccharides (endotoxin, LPS), cytokines, or ligation of CD40. Functional changes in response to inflammatory stimuli are mediated by induction of signaling cascades leading to activation of transcription factors and alterations in endothelial gene expression. This article summarizes the current knowledge of molecular events resulting in cytokine-mediated endothelial dysfunction.