Infusion of IL-10-expressing cells protects against renal ischemia through induction of lipocalin-2

Michaela Jung, Anna Sola, Jeremy Hughes, David C Kluth, Eugenia Vinuesa, Jose Luis Viñas, Albert Pérez-Ladaga, Georgina Hotter

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Ischemia/reperfusion injury is a leading cause of acute renal failure triggering an inflammatory response associated with infiltrating macrophages, which determine disease outcome. To repair the inflammation we designed a procedure whereby macrophages that overexpress the anti-inflammatory agent interleukin (IL)-10 were adoptively transferred. These bone marrow-derived macrophages were able to increase their intracellular iron pool that, in turn, augmented the expression of lipocalin-2 and its receptors. Infusion of these macrophages into rats after 1 h of reperfusion resulted in localization of the cells to injured kidney tissue, caused increases in regenerative markers, and a notable reduction in both blood urea nitrogen and creatinine. Furthermore, IL-10 therapy decreased the local inflammatory profile and upregulated the expression of pro-regenerative lipocalin-2 and its receptors. IL-10-mediated protection and subsequent renal repair were dependent on the presence of iron and lipocalin-2, since the administration of a neutralizing antibody for lipocalin-2 or administration of IL-10 macrophages pretreated with the iron chelating agent deferoxamine abrogated IL-10-mediated protective effects. Thus, adoptive transfer of IL-10 macrophages to ischemic kidneys blunts acute kidney injury. These effects are mediated through the action of intracellular iron to induce lipocalin-2.
Original languageEnglish
Pages (from-to)969-82
Number of pages14
JournalKidney International
Volume81
Issue number10
DOIs
Publication statusPublished - 2012

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