Human coronary endothelial cell activation by endotoxin is characterized by NF-kappa B activation and TNF-alpha synthesis
| Autor: | Sandra B. Haudek, Emily L. Chan, Brett P. Giroir, Joseph T. Murphy |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Lipopolysaccharides
Lipopolysaccharide Endothelium Transcription Genetic medicine.medical_treatment Critical Care and Intensive Care Medicine chemistry.chemical_compound Cytosol medicine Humans Nuclear protein Cells Cultured Cell Nucleus business.industry Tumor Necrosis Factor-alpha Monocyte NF-kappa B Molecular biology Coronary Vessels Endothelial stem cell Endotoxins Kinetics medicine.anatomical_structure Cytokine chemistry Cell culture Immunology Emergency Medicine Tumor necrosis factor alpha Endothelium Vascular business |
| Zdroj: | Shock (Augusta, Ga.). 16(5) |
| ISSN: | 1073-2322 |
| Popis: | Tumor necrosis factor-alpha (TNF-alpha), an early inflammatory mediator typically regulated by nuclear factor kappa B (NF-kappa B), plays a critical role in the development of cardiovascular dysfunction in sepsis. While several myocardial cell types synthesize TNF-alpha, the importance of the myocardial endothelium in sepsis-related cardiac cytokine production is unclear. To determine the role of the human coronary artery endothelial cell (HCA-EC) in the cytokine response to endotoxin we measured in vitro TNF-alpha synthesis, TNF-alpha mRNA, and the associated NF-kappa B response to LPS. To determine the magnitude of the HCA-EC response we assessed the TNF-alpha and NF-kappa B response to LPS in a human monocytic cell line (THP-1) as well. We observed an increase in supernatant TNF-alpha from LPS-stimulated HCA-EC (12 h) that was ablated by the proteosome inhibitor, ALLN (N-acetyl-Leu-Leu-norleucinal). Similarly, ALLN-sensitive TNF-alpha was produced by monocytes following LPS, although at concentrations 100-fold higher than HCA-EC. TNF-alpha mRNA from HCA-EC was detected at 60 min in LPS-stimulated cells, but not in unstimulated cells or cells pretreated with ALLN. NF-kappa B p50/p65 subunits were detectable in endothelial nuclear protein 60 min following LPS. In contrast, NF-kappa B subunits from monocytes were detected at 15 min. Also, while ALLN only attenuated endothelial NF-kappa B translocation, monocyte NF-kappa B translocation was completely inhibited. These data suggest endotoxin-stimulated human coronary endothelial cells express TNF-alpha, which is regulated in part by NF-kappa B activation, in a manner and degree distinct from human monocytes. |
| Databáze: | OpenAIRE |
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