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

Affiliations
  • 1Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Korea. bskim@mail.ulsan.ac.kr
  • 2Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-714, Korea.
  • 3Biomedical Research Center, Ulsan University Hospital, University of Ulsan, Ulsan 682-714, Korea.
  • 4School of Korean Medicine, Pusan National University, Pusan 626-870, Korea.

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
Full Text Links
  • EMM
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2021 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr