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

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.

The expression of LIGHT and HVEM in T lymphocytes post allo-HSCT and its relation to the development of GVHD / 中华器官移植杂志

Objective To explore the relationship between the expression of LIGHT/HVEM in patients after allo-HSCT and the development of GVHD. Methods The expression of LIGHT and HVEM in T lymphocytes was detected by FACS Calibur. Results All patients achieved engraftment and hematopoiesis reconstitution, aGVHD occurred in 9 of 26 patients (34.6%) with grade Ⅲ-Ⅳ aGVHD in 3 cases. Seven cases developed cGVHD (26.9%). LIGHT was not expressed in T lymphocytes from healthy donors and patients without GVHD, while constitutive expression of HVEM was detected. When aGVHD occurred, the expression levels of LIGHT in T lymphocytes were significantly increased, while those of HVEM decreased. After GVHD was controlled, the expression levels of those co-stimulators went back to normal On the day 15 after transplantation, the expression of LIGHT in T lymphocytes of patients with aGVHD later was significantly higher, while that of HVEM lower than in those without aGVHD. The patients with aGVHD of grades Ⅲ-Ⅳ demonstrated higher LIGHT expression than in those with aGVHD of grades Ⅰ-Ⅱ. Conclusion The expression of LIGHT and HVEM might be involved in the development of GVHD after allo-HSCT and could be used as one of the useful indicators in predicting aGVHD.