Inflammation plays a key role in the progression of cardiovascular disease, the leading cause of mortality in ESRD (end-stage renal disease). Over recent years, inflammation has been greatly reduced with treatment, but mortality remains high. The aim of the present study was to assess whether low (<2 pg/ml) circulating levels of IL-6 (interleukin-6) are necessary and sufficient to activate the transcription factor STAT3 (signal transducer and activator of transcription 3) in human hepatocytes, and if this micro-inflammatory state was associated with changes in gene expression of some acute-phase proteins involved in cardiovascular mortality in ESRD. Human hepatocytes were treated for 24 h in the presence and absence of serum fractions from ESRD patients and healthy subjects with different concentrations of IL-6. The specific role of the cytokine was also evaluated by cell experiments with serum containing blocked IL-6. Furthermore, a comparison of the effects of IL-6 from patient serum and rIL-6 (recombinant IL-6) at increasing concentrations was performed. Confocal microscopy and Western blotting demonstrated that STAT3 activation was associated with IL-6 cell-membrane-bound receptor overexpression only in hepatocytes cultured with 1.8 pg/ml serum IL-6. A linear activation of STAT3 and IL-6 receptor expression was also observed after incubation with rIL-6. Treatment of hepatocytes with 1.8 pg/ml serum IL-6 was also associated with a 31.6-fold up-regulation of hepcidin gene expression and a 8.9-fold down-regulation of fetuin-A gene expression. In conclusion, these results demonstrated that low (<2 pg/ml) circulating levels of IL-6, as present in non-inflamed ESRD patients, are sufficient to activate some inflammatory pathways and can differentially regulate hepcidin and fetuin-A gene expression.
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Research Article|
May 14 2010
A translational approach to micro-inflammation in end-stage renal disease: molecular effects of low levels of interleukin-6
Bruno Memoli;
*Department of Nephrology, University Federico II of Naples, 80131 Naples, Italy
Correspondence: Professor Bruno Memoli (email [email protected]).
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Simona Salerno;
Simona Salerno
†Institute of Membrane Technology, National Research Council of Italy (ITM-CNR), c/o University of Calabria, Rende 87030, Italy
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Alfredo Procino;
Alfredo Procino
*Department of Nephrology, University Federico II of Naples, 80131 Naples, Italy
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Loredana Postiglione;
Loredana Postiglione
‡Department of Cellular and Molecular Biology and Pathology, University Federico II of Naples, 80131 Naples, Italy
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Sabrina Morelli;
Sabrina Morelli
†Institute of Membrane Technology, National Research Council of Italy (ITM-CNR), c/o University of Calabria, Rende 87030, Italy
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Maria Luisa Sirico;
Maria Luisa Sirico
*Department of Nephrology, University Federico II of Naples, 80131 Naples, Italy
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Francesca Giordano;
Francesca Giordano
§Department of Cellular Biology, University of Calabria, Rende 87030, Italy
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Margherita Ricciardone;
Margherita Ricciardone
‡Department of Cellular and Molecular Biology and Pathology, University Federico II of Naples, 80131 Naples, Italy
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Enrico Drioli;
Enrico Drioli
†Institute of Membrane Technology, National Research Council of Italy (ITM-CNR), c/o University of Calabria, Rende 87030, Italy
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Vittorio E. Andreucci;
Vittorio E. Andreucci
*Department of Nephrology, University Federico II of Naples, 80131 Naples, Italy
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Loredana de Bartolo
Loredana de Bartolo
†Institute of Membrane Technology, National Research Council of Italy (ITM-CNR), c/o University of Calabria, Rende 87030, Italy
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Publisher: Portland Press Ltd
Received:
December 04 2009
Revision Received:
April 09 2010
Accepted:
April 09 2010
Accepted Manuscript online:
April 09 2010
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2010 Biochemical Society
2010
Clin Sci (Lond) (2010) 119 (4): 163–174.
Article history
Received:
December 04 2009
Revision Received:
April 09 2010
Accepted:
April 09 2010
Accepted Manuscript online:
April 09 2010
Citation
Bruno Memoli, Simona Salerno, Alfredo Procino, Loredana Postiglione, Sabrina Morelli, Maria Luisa Sirico, Francesca Giordano, Margherita Ricciardone, Enrico Drioli, Vittorio E. Andreucci, Loredana de Bartolo; A translational approach to micro-inflammation in end-stage renal disease: molecular effects of low levels of interleukin-6. Clin Sci (Lond) 1 August 2010; 119 (4): 163–174. doi: https://doi.org/10.1042/CS20090634
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