Cyclosporine Induces Endothelin-1 mRNA Synthesis and Nitric Oxide Production in Human Proximal Tubular Epithelial Cell Cultures
Autor: | Panagiotis Kotsantis, Dimitrios S. Goumenos, Evangelos Papachristou, John G. Vlachojannis, Athanasios Papadimitropoulos, Panagiotis Katsoris |
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Rok vydání: | 2009 |
Předmět: |
medicine.medical_specialty
Cell Nitric Oxide Critical Care and Intensive Care Medicine Nitric oxide Kidney Tubules Proximal chemistry.chemical_compound Chronic allograft nephropathy Internal medicine medicine Humans Cytotoxic T cell RNA Messenger Cells Cultured Cell Proliferation Probability Kidney Dose-Response Relationship Drug Endothelin-1 Reverse Transcriptase Polymerase Chain Reaction business.industry Epithelial Cells General Medicine medicine.disease Endothelin 1 Epithelium medicine.anatomical_structure Endocrinology chemistry Nephrology Cell culture Culture Media Conditioned Cyclosporine business |
Zdroj: | Renal Failure. 31:372-376 |
ISSN: | 1525-6049 0886-022X |
Popis: | Cyclosporine (CsA) is implicated in the development of chronic allograft nephropathy, which is related to reduced long-term allograft survival. The activation of tubular epithelial cells is involved in the renal scarring process via stimulation of factors such as endothelin-1 (ET-1) and nitric oxide (NO). The effect of CsA on the activation of tubular epithelial cells towards increased production of ET-1 and NO was investigated in this study.Human tubular epithelial cells (HK-2) were cultured in the presence of CsA at different concentrations (125, 250, 500, and 1,000 ng/mL). ET-1 m-RNA and NO production were measured using RT-PCR and Griess method, respectively. The cytotoxic effect of CsA was examined by the MTT method and cell count.A statistically significant and dose-dependent cytotoxic effect of cyclosporine on HK-2 cells was observed. A dose-dependent up-regulation of ET-1 mRNA production and NO accumulation was observed under the influence of CsA.Increased synthesis of endothelin-1 mRNA and nitric oxide as well as a significant cytotoxic effect on tubular epithelial cells under the influence of CsA might be related to the development of CsA nephrotoxicity. |
Databáze: | OpenAIRE |
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