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Title

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

AuthorsJung, Michaela ; Solà, Anna M. ; Vinuesa, Eugenia ; Viñas, Jose Luis ; Pérez Ladaga, Albert; Hotter, Georgina
Issue Date2012
PublisherInternational Society of Nephrology
CitationKidney International 81(10): 969-982 (2012)
AbstractIschemia/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. © 2012 International Society of Nephrology.
URIhttp://hdl.handle.net/10261/80748
DOI10.1038/ki.2011.446
Identifiersdoi: 10.1038/ki.2011.446
issn: 0085-2538
e-issn: 1523-1755
Appears in Collections:(IIBB) Artículos
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