Kawasaki syndrome (KS), an acute febrile illness of unknown etiology affecting infants and young children, is characterized by vascular inflammation of coronary arteries and other medium-sized muscular arteries, leading to coronary aneurysms. Treatment includes high-dose aspirin and intravenous gamma globulin. Cytokines elevated in KS include tumor necrosis factor-alpha (TNF-a ) and vascular endothelial growth factor (VEGF). Other molecules shown to be elevated in the acute phase of KS include adhesion molecule ICAM-1, together with the soluble forms of ICAM-1 and E-selectin. Adhesion molecules are expressed at low levels in the endothelium, but can be up-regulated when stimulated by inflammatory cytokines. Based on the above data, we hypothesized that elevated levels of TNF-a and VEGF observed in KS may increase the levels of adhesion molecules in vivo, allowing inflammatory and immune cells to adhere to the endothelium. To test this hypothesis, we determined if TNF-a and VEGF were capable of modulating the transcriptional activities of E-selectin, ICAM-1 and the monocyte chemoattractant protein-1 (MCP-1) in endothelial cells. In addition, we determined if gamma globulin, TGF-b or aspirin could block gene expression induced by TNF-a . Human umbilical vein endothelial cells (HUVEC) were cultured in 6-well plates and stimulated with 1 ng/mL TNF-a or 40 ng/mL VEGF, or pretreated with gamma globulin (10 mg/mL) prior to stimulation. RNA was extracted using RNAzol, and RNA reverse-transcribed into cDNA using oligo-dT. Gene-specific primers were then used to amplify E-selectin, ICAM-1, MCP-1 and GAPDH. Using semi-quantitative reverse transcription-polymerase chain reaction, we found that TNF-a at a concentration of 1 ng/mL up-regulated the expression of E-selectin, ICAM-1 and MCP-1 in HUVEC in a time- and dose-dependent manner (Figure 2). Pre-treatment of HUVEC with gamma globulin (10 mg/mL) did not inhibit the transcriptional activities of these adhesion molecules induced by TNF-a . VEGF (40 ng/mL) was unable to induce a significant increase in E-selectin or MCP-1 expression. These results indicate that TNF-a may play an important role in mediating increased levels of adhesion molecules in endothelial cells. Furthermore, MCP-1 may provide a gradient to attract monocytes to sites of inflammation, thus providing a mechanism by which immune and inflammatory cells home in and enter the extracellular matrix, thereby weakening the endothelium and hastening the process of aneurysm formation. Future studies are aimed at dissecting the effects of sodium salicylate, TGF-b in concert with gamma globulin on modulating adhesion molecule expression as well as the signaling events in coronary artery endothelial cells.