title: Herpesvirus entry mediator (HVEM) attenuates signals mediated by the lymphotoxin β receptor (LTβR) in human cells stimulated by the shared ligand LIGHT.
abstract: Signals mediated by members of the tumor necrosis factor receptor superfamily modulate a network of diverse processes including initiation of inflammatory responses and altering cell fate between pathways favoring survival and death. Although such pathways have been well-described for the TNF-α receptor, less is known about signaling induced by the TNF superfamily member LIGHT and how it is differentially altered by expression of its two receptors LTβR and HVEM in the same cell. We used cell lines with different relative expression of HVEM and LTβR to show that LIGHT-induced signals mediated by these receptors were associated with altered TRAF2 stability and RelA nuclear translocation. Production of the inflammatory chemokine CXCL10 was primarily mediated by LTβR. Higher expression of HVEM was associated with cell survival, while unopposed LTβR signaling favored pathways leading to apoptosis. Importantly, restoring HVEM expression in cells with low endogenous expression recapitulated the phenotype of cells with higher endogenous expression. Together, our data provide evidence that relative expression of HVEM and LTβR modulates canonical NF-κB and pro-apoptotic signals stimulated by LIGHT.
authors: Department of Pediatrics, Northwestern University Feinberg School of Medicine, Northwestern University, 310 East Superior Street, Morton 4-685, Chicago, IL 60611 USA.
authors: John
authors: J
authors: Bechill
authors: Department of Pediatrics, Northwestern University Feinberg School of Medicine, Northwestern University, 310 East Superior Street, Morton 4-685, Chicago, IL 60611 USA. Electronic address: wjmuller@northwestern.edu.
authors: William J
authors: WJ
authors: Muller
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D015870:Gene Expression / Q000502:physiology; D057809:HEK293 Cells; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects; D053259:Lymphotoxin beta Receptor / Q000502:physiology*; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000494:pharmacology / Q000502:physiology*; D020298:U937 Cells
chemical_list: C505697:LTBR protein, human; D008024:Ligands; D053259:Lymphotoxin beta Receptor; D053240:Receptors, Tumor Necrosis Factor, Member 14; C506028:TNFRSF14 protein, human; C505914:TNFSF14 protein, human; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D007371:Interferon-gamma
keywords: Apoptosis; Herpesvirus entry mediator (HVEM); LIGHT; Lymphotoxin beta receptor (LTβR); NF-kappa B (NF-κB); TNF receptor associated factor (TRAF)