Proinflammatory effects of LIGHT through HVEM and LTβR 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 beta receptor (LT beta R), herpes virus entry mediator (HVEM), and decoy receptor 3 (DcR3). LIGHT can induce either cell death and/or NF-kappa B activation via its interaction with LT beta R and/or HVEM. In this study, we investigated the effects of LIGHT in human umbilical vein endothelial cells (HUVECs). We demonstrated that both LT beta R and HVEM, but not DcR3, are present in HUVECs, and LIGHT can induce the secretion of chemokines (IL-8 and GRO-alpha), 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 beta R, could not induce the secretion of GRO-alpha, PGI(2), or the expression of COX-2. These results indicate that both LT beta R and HVEM can discriminatively mediate the expression of different genes in HUVECs, and suggest that LIGHT is a proinflammatory cytokine.