Proinflammatory effects of LIGHT through HVEM and LT β R interactions in cultured human umbilical vein endothelial cells

Members of the tumor necrosis factor (TNF) receptor (TNFR) superfamily are known to be potent mediators of immune responses. LIGHT is a member of the TNF superfamily, and its receptors have been identified as lymphotoxin β receptor (LTβR), herpes virus entry mediator (HVEM), and decoy receptor 3 (DcR3). LIGHT can induce either cell death and/or NF- κ B activation via its interaction with LTβR and/or HVEM. In this study, we investigated the effects of LIGHT in human umbilical vein endothelial cells (HUVECs). We demonstrated that both LT β R and HVEM, but not DcR3, are present in HUVECs, and LIGHT can induce the secretion of chemokines (IL-8 and GRO- α ), cell surface expression of adhesion molecules (ICAM-1 and VCAM-1), PGI 2 release, and COX-2 expression. However, the LIGHT mutein, LIGHT-R228E, which has been shown to exhibit binding specificity to LT β R, could not induce the secretion of GRO-α, PGI 2 , or the expression of COX-2. These results indicate that both LT β R and HVEM can discriminatively mediate the expression of different genes in HUVECs, and suggest that LIGHT is a proinflammatory cytokine.