Journal Article

Renal cells express a functional interleukin-15 receptor

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

in Nephrology Dialysis Transplantation

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

Volume 20, issue 3, pages 516-523
Published in print March 2005 | ISSN: 0931-0509
Published online January 2005 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfh616
Renal cells express a functional interleukin-15 receptor

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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 βγc subunits (IL-2/15Rβγc) and a unique high-affinity α-chain responsible for IL-15 specificity.

Methods. The cDNA of IL-15Rα 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-γ (IFN-γ), and mRNA and protein levels of IL-15R were determined. Jak–STAT tyrosine phosphorylation was assayed following IL-15 exposure.

Results. The full-length α-chain mRNA bearing exons 1–7 is expressed in TEC. IL-15Rα protein was detected on intact cells by flow cytometry and in extracts of human and mice renal cells using a specific anti-IL-15Rα 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-γ upregulated the α-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

Journal Article.  5064 words.  Illustrated.

Subjects: Nephrology

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