Recombinant, soluble LIGHT (HVEM ligand) induces increased IL-8 secretion and growth arrest in A375 melanoma cells

The heterotrimeric lymphotoxin alpha (1)beta (2) (LT alpha (1)beta (2)) com plex and LIGHT, a new member of the tumor necrosis factor (TNF) superfamily , have been identified as membrane-anchored ligands for the LT beta recepto r (LT betaR), a member of the TNF receptor (TNFR) superfamily. Although som e of the biologic activities of this receptor have been described using eit her soluble LT alpha (1)beta (2) as a ligand or agonistic monoclonal antibo dies (mAb), very little is known about the signaling of LIGHT via the LT be taR. To gain more insight into the biologic functions of LIGHT, we generate d a recombinant soluble form of human LIGHT (rsHuLIGHT). We demonstrate her e that this rsHuLIGHT is capable of binding to the LT betaR, Interestingly, receptor-mediated ligand precipitation analysis revealed that rsHuLIGHT bo und only to human LT betaR but not to mouse LT betaR, indicating a species- specific receptor ligand interaction. Activation of A375 human melanoma cel ls by rsHuLIGHT induced an increased secretion of interleukin-8 (IL-8). Fur thermore, rsHuLIGHT caused growth arrest of A375 cells even in the absence of interferon-gamma (IFN-gamma).