Nephrol Dial Transplant (2004) 19: 47-52
© ERA–EDTA 2003; all rights reserved
Original Article
Effects of mycophenolic acid on IL-6 expression of human renal proximal and distal tubular cells in vitro
Division of Nephrology, Department of Internal Medicine IV, J. W. Goethe-University, Frankfurt/M., Germany
Correspondence and offprint requests to: Patrick C. Baer, Johann Wolfgang Goethe University, Department of Internal Medicine IV, Division of Nephrology, Theodor-Stern-Kai 7, D-60590 Frankfurt/M., Germany. Email: p.baer{at}em.uni-frankfurt.de
Background. Interleukin-6 (IL-6) is a multifunctional cytokine which regulates immune responses and host defence mechanisms. IL-6 has been found to be increased in certain inflammatory conditions of the kidney, in which tubular epithelial cells play a pivotal role. Human renal tubular cells express IL-6. Until now no data about the effect of the immunosuppressant drug mycophenolic acid (MPA) on IL-6 expression were available.
Methods. Proximal and distal tubular epithelial cells (PTC/DTC) have been isolated immunomagnetically. Confluent monolayers were stimulated with interleukin-1ß (IL-1ß; 25 U/ml), IL-1ß+ MPA (0.25–50 µM) or MPA alone for 48 h. Release of IL-6 protein into the supernatant was evaluated with an enzyme immunoassay, IL-6 mRNA expression was evaluated using the Quantikine mRNA kit.
Results. After IL-1ß stimulation, a highly significant 2.6- (PTC) and 3.8-fold (DTC) upregulation of IL-6 expression was detectable. IL-6 mRNA was upregulated by IL-1ß [1.57- (PTC) and 2.03-fold (DTC)]. MPA inhibited this cytokine-induced IL-6 expression in a dose-dependent manner. Incubation with the lowest MPA concentration had no effect on the stimulated upregulation, whereas all higher doses significantly decreased IL-6 expression. Dexamethasone significantly inhibited the cytokine-induced IL-6 protein release in PTC, but not in DTC.
Conclusions. In this study we demonstrated for the first time an inhibitory effect of MPA on the stimulated IL-6 expression of renal tubular epithelial cells. In contrast to older data, which showed a synergistic upregulation of the expression of a CC-chemokine by a combination of cytokines and MPA, in the present study we could demonstrate an immunosuppressive effect of MPA on the expression of an important cytokine.
Keywords: distal tubule; epithelial cells; IL-6; kidney; mycophenolic acid; proximal tubule
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