Endothelial Cell Products as a Key Player in Hypoxia-Induced Nerve Cell Injury after Stroke.
- Author:
Chul Min CHO
1
;
Se Un HA
;
Hae Rahn BAE
;
Jae Taeck HUH
Author Information
1. Department of Neurosurgery, College of Medicine, Dong-A University, Busan, Korea. jthuh@donga.ac.kr
- Publication Type:Original Article
- Keywords:
Hypoxia;
Primary human umbilical vein endothelial cells;
Cytokines;
Endothelial permeability;
Neurotoxicity
- MeSH:
Anoxia;
Astrocytoma;
Blotting, Western;
Culture Media, Conditioned;
Cytokines;
Down-Regulation;
Endothelial Cells*;
Enzyme-Linked Immunosorbent Assay;
Humans;
Interleukin-1;
Interleukin-10;
Interleukin-6;
Interleukin-8;
Neuroblastoma;
Neurons*;
Nitric Oxide;
Permeability;
Reperfusion;
Stroke*;
Transforming Growth Factor beta;
Transforming Growth Factor beta1;
Tumor Necrosis Factor-alpha;
Umbilical Veins;
Vascular Endothelial Growth Factor A
- From:Journal of Korean Neurosurgical Society
2006;40(2):103-109
- CountryRepublic of Korea
- Language:English
-
Abstract:
OBJECTIVE: Activated endothelial cells mediate the cascade of reactions in response to hypoxia for adaptation to the stress. It has been suggested that hypoxia, by itself, without reperfusion, can activate the endothelial cells and initiate complex responses. In this study, we investigated whether hypoxia-induced endothelial products alter the endothelial permeability and have a direct cytotoxic effect on nerve cells. METHODS: Hypoxic condition of primary human umbilical vein endothelial cells(HUVEC) was induced by CoCl2 treatment in culture medium. Cell growth was evaluated by 3,4,5-dimethyl thiazole-3,5-diphenyl tetrazolium bromide (MTT) assay. Hypoxia-induced products (IL-1beta, TGF-beta1, IFN-gamma, TNF-alpha, IL-10, IL-6, IL-8, MCP-1 and VEGF) were assessed by enzyme-linked immunosorbent assay. Endothelial permeability was evaluated by Western blotting. RESULTS: Prolonged hypoxia caused endothelial cells to secrete IL-6, IL-8, MCP-1 and VEGF. However, the levels of IL-1, IL-10, TNF-alpha, TGF-beta, IFN-gamma and nitric oxide remained unchanged over 48 h hypoxia. Hypoxic exposure to endothelial cells induced the time-dependent down regulation of the expression of cadherin and catenin protein. The conditioned medium taken from hypoxic HUVECs had the cytotoxic effect selectively on neuroblastoma cells, but not on astroglioma cells. CONCLUSION: These results suggest the possibility that endothelial cell derived cytokines or other secreted products with the increased endothelial permeability might directly contribute to nerve cell injury followed by hypoxia.
