Antiinflammatory Effects of the ETS Factor ERG in Endothelial Cells Are Mediated Through Transcriptional Repression of the Interleukin-8 Gene

ERG (Ets-related gene) is an ETS transcription factor that has recently been shown to regulate a number of endothelial cell (EC)-restricted genes including VE-cadherin, von Willebrand factor, endoglin, and intercellular adhesion molecule-2. Our preliminary data demonstrate that unlike other ETS factors, ERG exhibits a highly EC-restricted pattern of expression in cultured primary cells and several adult mouse tissues including the heart, lung, and brain. In response to inflammatory stimuli, such as tumor necrosis factor-α, we observed a marked reduction of ERG expression in ECs. To further define the role of ERG in the regulation of normal EC function, we used RNA interference to knock down ERG. Microarray analysis of RNA derived from ERG small interfering RNA– or tumor necrosis factor-α–treated human umbilical vein (HUV)ECs revealed significant overlap ( P