The HVEM signaling pathway in monocytes

Herpes virus entry mediator (HVEM) is a member of the tumor necrosis factor receptor (TNFR) superfamily and is expressed on many immune cells. In this study we show that treatment of human monocytes with recombinant human LIGHT (rhLIGHT) induces rapid Ca²⁺ influx in an HVEM-specific manner in parallel with the TNF-alpha production and enhances the bactericidal activities of monocytes. Immunoprecipitation and Western blotting analysis revealed phosphorylation of phospholipase Cgamma₁(PLCgamma₁) but not PLCgamma₂. Silencing PLCgamma₁, or pre-incubation of monocytes with PLC inhibitors, antagonists of the inositol-1,4,5-triphosphate receptor or [Ca²⁺]_i inhibitors completely abolished rhLIGHT-induced Ca²⁺ influx. Our results indicate that Ca²⁺ is a downstream mediator of the LIGHT/HVEM interaction in monocytes.