Recombinant,Soluble LIGHT (HVEM Ligand) Induces Increased IL-8 Secretion and Growth Arrest in A375 Melanoma Cells

Abstract

The heterotrimeric lymphotoxin α₁β₂ (LTα₁β₂) complex and LIGHT, a new member of the tumor necrosis factor (TNF) superfamily, have been identified as membrane-anchored ligands for the LTβ receptor (LTβR), a member of the TNF receptor (TNFR) superfamily. Although some of the biologic activities of this receptor have been described using either soluble LTα₁β₂ as a ligand or agonistic monoclonal antibodies (mAb), very little is known about the signaling of LIGHT via the LTβR. To gain more insight into the biologic functions of LIGHT, we generated a recombinant soluble form of human LIGHT (rsHuLIGHT). We demonstrate here that this rsHuLIGHT is capable of binding to the LTβR. Interestingly, receptor-mediated ligand precipitation analysis revealed that rsHuLIGHT bound only to human LTβR but not to mouse LTβR, indicating a species-specific receptor ligand interaction. Activation of A375 human melanoma cells by rsHuLIGHT induced an increased secretion of interleukin-8 (IL-8). Furthermore, rsHuLIGHT caused growth arrest of A375 cells even in the absence of interferon-γ (IFN-γ).