Association between renal injury and reduced interleukin-15 and interleukin-15 receptor levels in acute kidney injury

Hadar Eini, Noa Tejman-Yarden, Eli C. Lewis, Cidio Chaimovitz, Moshe Zlotnik, Amos Douvdevani

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Interleukin (IL)-15 serves as a survival factor for a broad array of cells. Renal cells express both IL-15 and its receptor (IL-15R); however, the role of IL-15 in the kidney is yet to be determined. We examined IL-15 and IL-15R levels in sepsis-related renal injury, ischemia-reperfusion injury (IRI), and cisplatin-induced nephrotoxicity. To test the anti-apoptotic effect of IL-15, Bcl-2/Bax mRNA levels were assessed in kidneys of IL-15Rα-/- mice and in IL-15-stimulated renal epithelial cells (RECs). In addition, RECs were exposed to cisplatin and apoptosis was evaluated by TUNEL staining, caspase-3 activity, and cell cycle analysis. Intrarenal IL-15 levels decreased 24 h after initiation of all three examined pathologies by 5.8-fold (sepsis), 11-fold (IRI), and 23-fold (cisplatin-induced nephrotoxicity). Further experiments revealed that while addition of rIL-15 (1 ng/mL) to wild-type (WT) RECs increased Bcl-2/Bax ratio by 2-fold, kidneys of IL-15Rα-/- mice exhibited 4-fold lower Bcl-2/Bax ratio compared to WT mice. Accordingly, IL-15 lowered the apoptotic rate in cisplatin-treated cultured REC, and IL-15Rα-/- renal cells exhibited a higher rate of cisplatin-induced apoptosis. Furthermore, IL-15 levels negatively correlated with BUN of cisplatin-treated mice (R = -0.69, P = 0.003), suggesting that a decline in renal-derived IL-15 is detrimental to renal cell survival and kidney function during pathological stress.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalJournal of Interferon and Cytokine Research
Volume30
Issue number1
DOIs
StatePublished - 1 Jan 2010

ASJC Scopus subject areas

  • Immunology
  • Cell Biology
  • Virology

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