Renal cells express a functional interleukin-15 receptor.
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 betagammac subunits (IL-2/15Rbetagammac) and a unique high-affinity alpha-chain responsible for IL-15 specificity.


METHODS
The cDNA of IL-15Ralpha 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-15Ralpha protein was detected on intact cells by flow cytometry and in extracts of human and mice renal cells using a specific anti-IL-15Ralpha 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.
Tejman-Yarden
Noa
N
Nephrology Laboratory and Department of Nephrology, Soroka University Medical Center, P.O. Box 151, Beer-Sheva 84101, Israel.
Zlotnik
Moshe
M
Lewis
Eli
E
Etzion
Ohad
O
Chaimovitz
Cidio
C
Douvdevani
Amos
A
D000818:Animals; D000915:Antibody Affinity; D000918:Antibody Specificity; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D019409:Interleukin-15 / Q000276:immunology / Q000378:metabolism; D007672:Kidney Cortex / Q000166:cytology* / Q000378:metabolism*; D007679:Kidney Medulla / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
C508024:IL15RA protein, human; C508025:Il15ra protein, mouse; D019409:Interleukin-15; D020033:Protein Isoforms; D012333:RNA, Messenger; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2