Recombinant, soluble LIGHT (HVEM ligand) induces increased IL-8 secretion and growth arrest in A375 melanoma cells.
The heterotrimeric lymphotoxin alpha(1)beta(2) (LTalpha(1)beta(2)) complex and LIGHT, a new member of the tumor necrosis factor (TNF) superfamily, have been identified as membrane-anchored ligands for the LTbeta receptor (LTbetaR), a member of the TNF receptor (TNFR) superfamily. Although some of the biologic activities of this receptor have been described using either soluble LTalpha(1)beta(2) as a ligand or agonistic monoclonal antibodies (mAb), very little is known about the signaling of LIGHT via the LTbetaR. 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 LTbetaR. Interestingly, receptor-mediated ligand precipitation analysis revealed that rsHuLIGHT bound only to human LTbetaR but not to mouse LTbetaR, 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-gamma (IFN-gamma).
Hehlgans
T
T
Institute of Pathology/Tumor Immunology, University of Regensburg, F.-J.-Strauss-Allee 11, D-93042 Regensburg, Germany.
Männel
D N
DN
D000818:Animals; D019556:COS Cells; D006131:Growth Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism*; D008024:Ligands; D008233:Lymphotoxin-alpha / Q000235:genetics / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology* / Q000517:prevention & control; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D011485:Protein Binding / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology*; D012995:Solubility; D014162:Transfection; D014407:Tumor Cells, Cultured; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D015854:Up-Regulation
D006131:Growth Inhibitors; D007141:Immunoglobulin Fc Fragments; D016209:Interleukin-8; D008024:Ligands; D008233:Lymphotoxin-alpha; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; C506028:TNFRSF14 protein, human; C505914:TNFSF14 protein, human; C506029:Tnfrsf14 protein, mouse; C505915:Tnfsf14 protein, mouse; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha