Journal Article

Effects of mycophenolic acid on IL-6 expression of human renal proximal and distal tubular cells <i>in vitro</i>

Patrick C. Baer, Binytha Wegner and Helmut Geiger

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 19, issue 1, pages 47-52
Published in print January 2004 | ISSN: 0931-0509
Published online January 2004 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfg429
Effects of mycophenolic acid on IL-6 expression of human renal proximal and distal tubular cells in vitro

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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-1β (IL-1β; 25 U/ml), IL-1β+ 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-1β 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-1β [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

Journal Article.  4184 words.  Illustrated.

Subjects: Nephrology

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