Indoxyl Sulfate Upregulates Expression of ICAM-1 and MCP-1 by Oxidative Stress-Induced NF-ĸB Activation
| Autor: | Zohra Tumur, Hitoshi Miyazaki, Hidehisa Shimizu, Atsushi Enomoto, Toshimitsu Niwa |
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| Rok vydání: | 2010 |
| Předmět: |
Time Factors
Intercellular Adhesion Molecule-1 Pharmacology CCL2 medicine.disease_cause Models Biological Antioxidants Humans Medicine RNA Messenger Risk factor Cells Cultured Chemokine CCL2 ICAM-1 Dose-Response Relationship Drug business.industry NF-kappa B medicine.disease Acetylcysteine Endothelial stem cell Oxidative Stress Gene Expression Regulation Nephrology Immunology Indoxyl Sulfate Endothelium Vascular Reactive Oxygen Species business Indican Oxidative stress Kidney disease |
| Zdroj: | American Journal of Nephrology. 31:435-441 |
| ISSN: | 1421-9670 0250-8095 |
| DOI: | 10.1159/000299798 |
| Popis: | Background/Aim: Indoxyl sulfate, a uremic toxin, is considered a risk factor for cardiovascular disease (CVD) in chronic kidney disease (CKD). The present study aimed to determine whether indoxyl sulfate increases the expression of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemotactic protein-1 (MCP-1) by reactive oxygen species (ROS)-induced activation of nuclear factor-ĸB (NF-ĸB) in vascular endothelial cells. Methods: Human umbilical vein endothelial cells (HUVEC) were incubated with indoxyl sulfate. The expression of ICAM-1 and MCP-1 in HUVEC was analyzed by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Phospho-NF-ĸB p65 (Ser 536), an active form of the NF-ĸB subunit, was determined by Western blotting. Results: Indoxyl sulfate significantly increased the mRNA expression of ICAM-1 and MCP-1 in HUVEC in a time- and concentration-dependent manner. Inhibitors of NF-ĸB (ammonium pyrrolidinedithiocarbamate and isohelenin) and an antioxidant (N-acetyl-L-cysteine) suppressed the indoxyl sulfate-induced expression of ICAM-1 and MCP-1 in HUVEC. Indoxyl sulfate increased phospho- NF-ĸB p65 in HUVEC, and N-acetyl-L-cysteine suppressed it. Conclusions: Indoxyl sulfate upregulates the expression of ICAM-1 and MCP-1 by ROS-induced activation of NF-ĸB in vascular endothelial cells. Thus, indoxyl sulfate may play an important role in the development of CVD in CKD by increasing the endothelial expression of ICAM-1 and MCP-1. |
| Databáze: | OpenAIRE |
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