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NDT Advance Access published online on January 25, 2005
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfh616
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Nephrol Dial Transplant © ERA-EDTA 2004; all rights reserved
Received June 23, 2004
Accepted November 3, 2004

Original Articles

Renal cells express a functional interleukin-15 receptor

Noa Tejman-Yarden 1, Moshe Zlotnik 1, Eli Lewis 2, Ohad Etzion 2, Cidio Chaimovitz 2, and Amos Douvdevani 2*

1 Department of Nephrology, Soroka University Medical Center, Ben-Gurion University of the Negev, Faculty of Health Sciences, Beer-Sheva, Israel; The authors wish it to be known that, in their opinion, the first two authors contributed equally to this work
2 Department of Nephrology, Soroka University Medical Center, Ben-Gurion University of the Negev, Faculty of Health Sciences, Beer-Sheva, Israel

* To whom correspondence should be addressed.
Amos Douvdevani, E-mail: amosd{at}bgu.ac.il



  Abstract

Background. Interleukin (IL)-15 is a pleiotropic cytokine known to be involved in graft rejection and to serve as a survival factor for leukocytes and epithelial cells, including renal cells. It utilizes a heterotrimeric receptor complex that consists of the IL-2 receptor {beta}{gamma}c subunits (IL-2/15R{beta}{gamma}c) and a unique high-affinity {alpha}-chain responsible for IL-15 specificity.

Methods. The cDNA of IL-15R{alpha} main mRNA product was isolated from primary human tubular epithelial cells (TEC) and sequenced. IL-15R expression in TEC and in murine renal tissue was demonstrated using western blotting, ligand binding and flow cytometry. TEC were activated with combinations of IL-15, IL-2 and interferon-{gamma} (IFN-{gamma}), and mRNA and protein levels of IL-15R were determined. Jak-STAT tyrosine phosphorylation was assayed following IL-15 exposure.

Results. The full-length {alpha}-chain mRNA bearing exons 1-7 is expressed in TEC. IL-15R{alpha} protein was detected on intact cells by flow cytometry and in extracts of human and mice renal cells using a specific anti-IL-15R{alpha} antibody and by ligand-binding assay. The three subunits of the IL-15R were similarly expressed in cortex and medulla of mice kidney. Stimulation of TEC with IFN-{gamma} upregulated the {alpha}-chain while IL-2 and IL-15 had no effect on its expression. A short IL-15 stimulation of TEC induced tyrosine phosphorylation of the main IL-15 signalling molecules (Jak-1, Jak-3, STAT-3 and STAT-5).

Conclusions. Our data demonstrate the presence of a functional IL-15 receptor in the kidney. Since renal cells produce IL-15, this cytokine may have an autocrine/paracrine regulatory role in the kidney.

Keywords: interleukin-15; interleukin-15 receptor; Jak; STAT; tubular epithelial cells.
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