Exp Mol Med.  2012 Feb;44(2):149-158. 10.3858/emm.2012.44.2.010.

The presence of high level soluble herpes virus entry mediator in sera of gastric cancer patients

• Heo SK
• Ju SA
• Kim GY
• Park SM
• Back SH
• Park NH
• Min YJ
• An WG
• Nguyen TH
• Kim SM
• Kim BS

• KMID: 1120133
• DOI: http://doi.org/10.3858/emm.2012.44.2.010

Abstract

The development of gastric cancer (GC) is closely related to chronic inflammation caused by Helicobacter pylori infection, and herpes virus entry mediator (HVEM) is a receptor expressed on the surface of leukocytes that mediates potent inflammatory responses in animal models. However, the role of HVEM in human GC has not been studied. Previously, we showed that the interaction of HVEM on human leukocytes with its ligand LIGHT induces intracellular calcium mobilization, which results in inflammatory responses including induction of proinflammatory cytokine production and anti-bacterial activities. In this study, we report that leukocytes from GC patients express lower levels of membrane HVEM (mHVEM) and have lower LIGHT-induced bactericidal activities than those from healthy controls (HC). In contrast, levels of soluble HVEM (sHVEM) in the sera of GC patients were significantly higher than in those of HC. We found that monocyte membrane-bound HVEM is released into the medium when cells are activated by proinflammatory cytokines such as TNF-alpha and IL-8, which are elevated in the sera of GC patients. mHVEM level dropped in parallel with the release of sHVEM, and release was completely blocked by the metalloprotease inhibitor, GM6001. We also found that the low level of mHVEM on GC patient leukocytes was correlated with low LIGHT-induced bactericidal activities against H. pylori and S. aureus and production of reactive oxygen species. Our results indicate that mHVEM on leukocytes and sHVEM in sera may contribute to the development and/or progression of GC.

Keyword

cytokines; inflammation; monocytes; receptors, tumor necrosis factor, member 14; stomach neoplasms; TNFSF14 protein, human

MeSH Terms

Aged
Cells, Cultured
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
Humans
Male
Middle Aged
Monocytes/metabolism
Neutrophils/metabolism
Reactive Oxygen Species/metabolism
Receptors, Tumor Necrosis Factor, Member 14/*blood
Stomach Neoplasms/*blood/metabolism
Tumor Necrosis Factor Ligand Superfamily Member 14/blood