Vascular endothelium, situated at the boundary between blood and tissues, is now known to play a critical role in the inflammatory process through recruiting immune cells into tissues and sites of inflammation. Lipopolysaccharide (LPS), endotoxic component extracted from the cell wall of gram-negative bacteria, stimulates endothelial cells to activate the nuclear transcription factor NF-κB and induce various adhesion molecules and inflammatory mediators. Among the anti-apoptotic genes activated by NF-κB, transcripts for inhibitor of apoptosis proteins (IAPs) are rapidly induced in response to LPS and delay apoptosis through direct and indirect inhibition of caspase activity. In the present study we carried out cDNA microarray analysis to elucidate how LPS alters program of gene expression of human umbilical vein endothelial cells (HUVECs) and to identify genes that are differentially expressed in HUVECs cultured with LPS as a mimicκing of pathologic and physiologic inflammatory conditions in vitro. From the analysis of cDNA microarray together with Northern blotting and semi-quantitative RT-PCR, we identified dramatically upregulated both previously reported and undiscovered transcripts for adhesion molecules, inflammation/chemoκines, transcription factors and anti-apoptotic proteins in LPS-stimulated HUVECs. In addition, we simultaneously identified anti-inflammatory, anti-oxidative stress and pro-apoptotic genes highly upregulated by LPS treatment in HUVECs. Surprisingly, although cIAP-1, cIAP-2 and XIAP transcripts were highly upregulated, their expression of endogenous proteins were not increased in HUVECs stimulated with LPS indicating the existence of yet undiscovered transcriptional or translational mechanisms may control expression and regulation of IAPs. The data presented here therefore suggest that when endothelial cells are challenged by inflammatory stimuli such as LPS, they undergo functional changes not only for the proinflammatory but also for the anti-inflammatory states and these may further be controlled by particular cellular or environmental signals in vascular pathological and physiological diseases.

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