title: The presence of high level soluble herpes virus entry mediator in sera of gastric cancer patients.
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-α 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.
authors: Department of Biological Sciences University of Ulsan Ulsan 680-749, Korea.
authors: Sook-Kyoung
authors: SK
authors: Heo
authors: Seong-A
authors: SA
authors: Ju
authors: Gyu Yeol
authors: GY
authors: Kim
authors: Sang-Min
authors: SM
authors: Park
authors: Sung Hun
authors: SH
authors: Back
authors: Neung-Hwa
authors: NH
authors: Park
authors: Young Joo
authors: YJ
authors: Min
authors: Won G
authors: WG
authors: An
authors: Thi Thu-Ha
authors: TT
authors: Nguyen
authors: Sun-Min
authors: SM
authors: Kim
authors: Byung-Sam
authors: BS
authors: Kim
mesh_terms: D000368:Aged; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000097:blood*; D013274:Stomach Neoplasms / Q000097:blood* / Q000378:metabolism; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000097:blood
chemical_list: D017382:Reactive Oxygen Species; D053240:Receptors, Tumor Necrosis Factor, Member 14; C505914:TNFSF14 protein, human; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14