Genistein inhibits human TNF-α-induced porcine endothelial cell adhesiveness for human monocytes and natural killer cells |
| |
作者单位: | National Laboratory of Biomembrane and Membrane Biotechnology,Institute of Zoology, Chinese Academy of Sciences, Beijing 100080,China
|
| |
摘 要: | Cellular immune response is a major barrier to xenotransplantation. Human tumor necrosis factor-α (hTNF-α) possesses cross-species activity and directly amplifies the immune rejection via the upregulation of adhesion molecules on porcine endothelium. We investigated the role of protein tyrosine phosphorylation in the induction of expression of E-sclectin and vascular cell adhesion molecule-1 (VCAM-1), and the augmentation of adhesion of human peripheral blood monocytes (PBMo) and natural killer cells (PBNK), after rhTNF-α-stimulation of porcine aortic endothelial cells (PAEC) in vitro, rhTNF-α-increased adhesiveness of PAEC for both PBMo and PBNK was dose-dependently reduced by pretreatment of PAEC with the selective protein tyrosine kinase (PTK) inhibitor genistein. The inhibitory effect occurred at the early time of PAEC activation triggered by rhTNF-α, and was completely reversible. PTK activity assay indicated that genistein also suppressed rhTNF-α stimulated activation of protein tyrosine kinases (PTKs) in PAEC in a dose-dependent manner. Flow cytometric analysis showed that genistein inhibited the upregulation of E-selectin and VCAM-1 by rhTNF-α. These results suggest that PTKs may regulate the expression of E-selectin and VCAM-1 on PAEC and the adherence of PBMo and PBNK induced by rhTNF-α. Moreover, dietary genistein, used as an adhesion antagonist, may contribute to managing the cell-mediated rejection in the clinical application.
|
关 键 词: | human tumor necrosis factor-α (hTNF-α) |
Genistein inhibits human TNF-α-induced porcine endothelial cell adhesiveness for human monocytes and natural killer cells |
| |
Authors: | Xiaofeng Zhang Yan Gu Zhimin Feng Liqin Ban Meifu Feng |
| |
Institution: | (1) National Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, 100080 Beijing, China |
| |
Abstract: | Cellular immune response is a major barrier to xenotransplantation. Human tumor necrosis factor-α (hTNF-α) possesses cross-species
activity and directly amplifies the immune rejection via the upregulation of adhesion molecules on porcine endothelium. We
investigated the role of protein tyrosine phosphorylation in the induction of expression of E-selectin and vascular cell adhesion
molecule-1 (VCAM-1), and the augmentation of adhesion of human peripheral blood monocytes (PBMo) and natural killer cells
(PBNK), after rhTNF-α-stimulation of porcine aortic endothelial cells (PAEC) in vitro. rhTNF-α-increased adhesiveness of PAEC for both PBMo and PBNK was dose-dependently reduced by pretreatment of PAEC with the
selective protein tyrosine kinase (PTK) inhibitor genistein. The inhibitory effect occurred at the early time of PAEC activation
triggered by rhTNF-α, and was completely reversible. PTK activity assay indicated that genistein also suppressed rhTNF-α stimulated
activation of protein tyrosine kinases (PTKs) in PAEC in a dose-dependent manner. Flow cytometric analysis showed that genistein
inhibited the upregulation of E-selectin and VCAM-1 by rhTNF-α. These results suggest that PTKs may regulate the expression
of E-selectin and VCAM-1 on PAEC and the adherence of PBMo and PBNK induced by rhTNF-α. Moreover, dietary genistein, used
as an adhesion antagonist, may contribute to managing the cell-mediated rejection in the clinical application. |
| |
Keywords: | genistein porcine aortic endothelial cells (PAEC) human peripheral blood monocytes (PBMo) human peripheral blood natural killer cells ( PBNK) cell adhesion |
本文献已被 万方数据 SpringerLink 等数据库收录! |
| 点击此处可从《中国科学通报(英文版)》浏览原始摘要信息 |
| 点击此处可从《中国科学通报(英文版)》下载免费的PDF全文 |