HVEM signaling in monocytes is mediated by intracellular calcium mobilization
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- HVEM signaling in monocytes is mediated by intracellular calcium mobilization
- Heo, Sook-Kyoung; Yoon, Min-A; Lee, Sang-Chul; Ju, Seong-A; Choi, Jang Hyun; Suh, Pann-Ghill; Kwon, Byoung S.; Kim, Byung-Sam
- EPIDERMAL-GROWTH-FACTOR; PHOSPHOLIPASE-C-GAMMA; PLECKSTRIN HOMOLOGY DOMAIN; LYMPHOTOXIN BETA-RECEPTOR; TYROSINE PHOSPHORYLATION; DYNAMIN BINDS; SH3 DOMAINS; LIGHT; CELLS; C-GAMMA-1
- Issue Date
- AMER ASSOC IMMUNOLOGISTS
- JOURNAL OF IMMUNOLOGY, v.179, no.9, pp.6305 - 6310
- Herpes virus entry mediator (HVEM) is a member of the TNF receptor (TNFR) superfamily and is expressed on many immune cells, including T and B cells, NK cells, monocytes, and nentrophils. Interaction of HVEM with its ligand, LIGHT, costimulates T cells and increases the bactericidal activity of monocytes and neutrophils. The interaction recruits cytoplasmic TNFR-associated factor adaptor proteins to the intracellular domain of HVEM. This leads to NF kappa B activation as a result of I kappa B alpha degradation and/or JNK/AP-1 activation, and ultimately results in the expression of genes required for cell survival, cytokine production, or cell proliferation. In this study, we show that treatment of human monocytes with recombinant human LIGHT (rhLIGHT) induces rapid elevation of intracellular calcium concentration ([Ca2+](i)) in a HVEM-specific manner in parallel with TNF-alpha production, and enhances the bactericidal activities of monocytes. Immunoprecipitation and Western blotting analyses revealed phosphorylation of phospholipase C gamma 1 (PLC-gamma 1) but not PLC gamma 2. rhLIGHT-induced Ca2+ response was completely abolished by silencing PLC gamma 1, or preincubating monocytes with PLC inhibitors, antagonists of the inositol-1,4,5-triphosphate receptor, or [Ca2+](i) chelators. Furthermore, these PLC/Ca2+ inhibitors also blocked rhLIGHT-mediated I kappa B alpha degradation, generation of reactive oxygen species, TNF-a production and the bactericidal activities of monocytes. Our results indicate that Ca(2+)is a downstream mediator of the LIGHT/HVEM interaction in monocytes.
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