Bacterial lipopolysaccharides (LPS) induce expression of multiple genes in endothelial cells, which are critical cellular effectors in various pathologic syndromes. Using subtractive hybridization to identify genes that are differentially induced in human endothelial cells treated with LPS, we found that retinoic acid-inducible gene I (RIG-1) is induced in endothelial cells stimulated with LPS. RIG-1 encodes a protein belonging to the DExH-box family which has diverse roles in regulation of gene expression and cellular functions. Cyclooxygenase-2 (COX-2) is also induced in endothelial cells by LPS. Overexpression of RIG-1 selectively upregulated expression of COX-2 and also induced COX-2 promoter activity. RIG-1 is an inducible gene in stimulated endothelial cells that may have important roles in vascular pathology by virtue of its ability to regulate expression of the COX-2 gene product. (C) 2002 Elsevier Science (USA).